Objective: To explore the alteration of plasma metabolomic profiles, screen the new serum markers of multidrug resistant epithelial ovarian cancer (EOC), and investigate the mechanism. Methods: The serum of 132 cases with cisplatin-resistant EOC, cisplatin-sensitive EOC, benign ovarian cyst and healthy donors were collected. Differentially plasma metabolic profiles were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The significantly different metabolites of each group were screened by using principal component analysis. Then compounds that played a key role in cisplatin resistance were identified by using nuclear magnetic resonance (NMR). The relationships between these compounds and clinical characteristics and prognosis were analyzed. Results: LC-MS/MS identified 25 800 metabolic compounds. According to the descending dimension algorithm by principal component analysis, six compounds which were the biggest contributor to grouping were identified. The identified results of NMR showed that the serum level of C16 Sphinganine was lower while Dodemorph was higher in the EOC than those of the normal control. Compared to the cisplatin sensitive group, cisplatin resistant group exhibited a specific metabolic trait characterized by upregulation of 1-Monopalmitin, Ricinoleic acid methyl ester, Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate and downregulation of Calycanthidine. The four components were all associated with fatty acid metabolism, and the combinational diagnostic sensitivity of these biomarkers for cisplatin-resistance was 86.50% and the specificity was 81.80%, the area of receiver operating characteristic (ROC) curve was 0.93. Conclusions: The metabolic signatures of normal control, benign ovarian cyst, cisplatin sensitivity and cisplatin resistance can be clearly separated from each other by LC-MS/MS technology.The combinational four biomarkers including Calycanthidine, 1-Monopalmitin, Ricinoleic acid methl ester and Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate are more sensitive and specific for the diagnosis of cisplatin resistant EOC, and may provide the potentially predict markers of chemotherapeutic response in metabolic level. The fatty acid metabolism may participate in the cisplatin resistant progression of EOC.

Objective: To investigate the influences of bone marrow stromal cells, components of extracellular matrix and cytokine secreted by stromal cells on the chemotherapeutic sensitivity of acute lymphoblastic leukemia cells to cytosine arabinoside (Ara-C). Methods: The co-culture model of acute lymphoblastic leukemia cell Sup-B15 and bone marrow stromal cell OP9 was constructed. Sup-B15 cells were cultured alone or co-cultured with OP9 cells, inactivated OP9 cells, the conditional medium (CM) of co-cultured OP9 cells and Sup-B15 cells, the CM of OP9 cells alone or Sup-B15 cells alone, respectively. The effects of different concentrations of Ara-C on the proliferation of each Sup-B1 cell group mentioned above were detected by cell counting kit-8 (CCK-8) method. The effects of different concentrations of Ara-C on the apoptosis of each group were detected by flow cytometry (FCM). The expressions of Bcl-2 protein in each group were detected by western blot. Results: The results of CCK-8 test showed that the inhibitory efficiency of Ara-C was in a dose-dependent manner. With different concentrations of Ara-C treatment for 48 hours, the half maximal inhibitory concentrations (IC(50)) of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were 0.510 and 0.339 μg/ml, respectively, significantly higher than 0.091 μg/ml of Sup-B15 cultured alone group (P<0.05). The IC(50) of CM of Sup-B15 and OP9 co-cultured group was 0.204 μg/ml, significantly higher than 0.087 μg/ml of the CM of OP9 cultured alone group (P<0.05) and 0.097 μg/ml of the CM of Sup-B15 cultured alone group (P<0.05). The results of flow cytometry showed that with 0.10 μg/ml Ara-C treatment for 24 hours, the early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group and Sup-B15 cultured alone group were (6.67±2.19) %, (8.95±3.04) % and (20.46±2.63) %, respectively. The early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were significantly lower than that of Sup-B15 cultured alone group (P<0.05). The early apoptotic cell percentages of the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were (11.16±2.97)%, (22.08±2.71)% and (19.25±1.57)%, respectively, the former two of which were significantly lower than the last one (P<0.05). The results of western blot showed that the relative expression levels of Bcl-2 protein of Sup-B15 cultured alone group, Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group, the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were 1.00±0.00, 1.53±0.03, 1.38±0.01, 1.26±0.05, 1.03±0.01 and 0.98±0.02, respectively. The expression levels of bcl-2 protein of three combined groups were significantly higher than that of Sup-B15 cultured alone group (P<0.05). while no statistically significant difference was observed between the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group (P>0.05). Conclusion: Bone marrow stromal cell OP9, the components of bone marrow extracellular matrix and cytokine secreted by stromal cells are involved in the induction of the chemotherapeutic resistance of Sup-B15 cells to Ara-C.

To study sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi, ten sesquiterpenes ,zedoarofuran (1), chlorajapolide D (2), 4β, 8β-dihydroxy-5α(H)-eudesm-7(11)-en-8, 12-olide (3), curcolonol (4), lasianthuslactone A (5), chlomultin C (6), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4, 7(11) -trieno-12, 8-lactone (7), shizukanolide E (8) , shizukanolide F (9) , 9α-hydroxycurcolonol (10), and five bis-sesquiterpenes, shizukaol B (11), shizukaol C (12) , cycloshizukaol A (13) , sarcandrolide B (14) , henriol A(15), were isolated by using different kinds of column chromatography methods from the ethyl acetate part of Ch.henryi and their structures were identified based on spectroscopic methods. Compounds 2, 8, 9, and 10 were obtained from the genus Chloranthus for the first time. Compounds 2, 5, 8-10, 12,and 14 were obtained from this plant for the first time. Some isolated compounds were subjected to evaluate the anti-metastasis breast cancer activity by using pharmacological methods, and only compounds 4, 11, and 12 were potent active.

Components that systematic separated from the root of Anaycclus pyrethrum were identified, in order to lay a foundation for future study of the root of A. pyrethrum. The CCK-8 assay showed that dichloromethane fraction exhibited the highest degree of cytotoxicity than others. Ten monomeric components were obtained from dichloromethane fraction and ethyl acetate fraction extracted from the root of A. pyrethrum, including 7 N-alkylamides, one coumarin and two flavonoid glycosides. They were identified as tetradeca-2E,4E,8E-trienoic acid 4-hydroxyphenylethylamide(1), deca-2E,4E-dienoicacid isobutylamide(2), undeca-2E,4E-diene-8,10-diynoic acid phenylethylamide(3), tetradeca-2E,4E-dienoic acid 4-hydroxyphenylethylamide(4), tetradeca-2E,4E-diene-8,10-diynoic acid isobutylamide(5), deca-2E,4E- dienoic acid 4-hydroxyphenylethylamide(6), dodeca-2E,4E-dienoic acid 4-hydroxy -phenyl-ethylamide(7), isoscopoletin(8), quercetin-7-O-β-D-glucopyranoside(9), isorhamnetin-7-O-β-D-glucopyranoside(10). Among them, compound 1 was identified as a new compound, Compounds 2-4, 8-10 were isolated from this herb for the first time.

Dried stem bark from Albizia julibrissin(AJ) is a common traditional Chinese herb with several therapy effects including insomnia, anxiety and anti-tumor. Recently, the anti-tumor effect and mechanism studies of AJ have drawn much attention; however, there are still some troubles in chemical composition separation, which leads to the difficulties in pharmacological research of AJ. In this study, we firstly confirmed the proliferation inhibitory effect of total saponins from AJ(TSAJ)on human hepatocarcinoma(HepG2) cells, and also tested the apoptosis induction effect of TSAJ. Then, we successfully captured the potential target proteins from HepG2 lysates by using TSAJ-modified solid beads, and identified the target proteins by LC-MS/MS. Finally, we confirmed 5 target proteins including Exportin-2, Beta-actin-like protein 2, Myosin-9, Protein transport protein Sec61 subunit beta,and Cytochrome c oxidase copper chaperone, which are responsible forcell apoptosis, proliferation, differentiation andmigration. In summary, our findings elucidate the potential anti-tumor mechanism of TSAJ from the direct target proteins, and provide a new insight for exploring the pharmacological mechanism of traditional Chinese medicine.

To observe the effectiveness and safety of electrothermal acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in the cancerous patients of phlegm-stasis interaction in cisplatin-containing chemotherapy.

To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits.
 Methods: Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each): doxorubicin (DOX) group, DOX-LIP group, SPIO-DOX group, and SPIO-DOX-LIP group. Liver function (AST and ALT) was measured at 0, 1, 3, 5 and 7 d after transhepatic arterial embolization. The serum DOX level was measured at 0, 5, 15, 30, 60, and 120 minutes after transhepatic arterial embolization. MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group, while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group. All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level. The histopathologic examinations were performed including HE staining, Prussian blue staining and TUNEL assay, and then the tumor necrosis percentage and apoptosis index were calculated.
 Results: Compared to the DOX group, the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P<0.05). The levels of ALT and AST in the DOX group, DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7, there were no significant differences (P>0.05). The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P<0.05). However, the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P<0.05). The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7. Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images. Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group, and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P<0.05).
 Conclusion: This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor. It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.

Isocorydine and its analogs were extracted from Dicranostigma leptopodum and Stephania yunnanensis through the method of natural products chemistry. Its derivatives were prepared by chemical structure modifications from isocorydine. MTT method was used to study the inhibitory effect of those compounds on the growth of HepG2, HeLa and MGC-803 cancer cell lines in vitro. The results showed that isocorydine and its analogs all have the growth inhibition for those cancer cell lines. This paper investigated the structure-activity relationship of isocorydine and its derivatives with anticancer activity in the aspect of stereochemical structure, functional groups positions of the compounds and the electron density of aromatic rings based on the single crystal diffraction structure and the molecular docking of EGFR and isocorydine.

Objective To investigate the effect of short hairpin RNA (shRNA) knockdown of arachidonate 5-lipoxygenase (Alox5) gene on the apoptosis of resistant chronic myeloid leukemia K562/ADM cells. Methods Three pairs of shRNA fragment targeting human Alox5 gene were synthesized and inserted into pGenesil-1 interference vector. Enzyme digestion and sequencing were performed to identify the recombinant plasmid pGenesil-1-shRNA-Alox5. The plasmid was then transfected into K562/ADM cells. Real-time quantitative PCR and Western blotting were used to detect the Alox5 mRNA and protein levels to get the best interference group. The pGenesil-1-shRNA-Alox5 plasmid group with higher interference efficiency was selected as the experimental subjects. Real-time quantitative PCR was adopted to detect the expression level of bcr/abl mRNA and Western blotting to detect the BCR/ABL fusion protein, and the apoptotic rate was assessed by flow cytometry. Results The enzyme digestion and sequencing confirmed the successful construction of recombinant plasmid. Compared with the negative pGenesil-1-K562/ADM control group and blank K562/ADM cell group, the Alox5 mRNA and protein levels of K562/ADM cells transfected with pGenesil-1-shRNA-Alox5 recombinant plasmid significantly decreased, and after the knockdown of Alox5, the levels of bcr/abl mRNA and BCR/ABL fusion protein significantly decreased and the apoptosis rate increased obviously. Conclusion The knockdown of Alox5 gene can induce the decreased levels of bcl/abl mRNA and BCR/ABL fusion protein in the K562/ADM cells and increased apoptosis rate.

Objective To investigate the effect of lentivirus-mediated shRNA targeting AKT1 gene on the sensitivity of gastric cancer xenografts to doxorubicin. Methods To establish the lentiviral vector of AKT1 RNA interference (RNAi), the vector of pGCSIL-shAKT1-GFP was infected into HEK293T cells, and meanwhile, the empty vector pGCSIL-shCON-GFP was assigned as a blank group, and then the viruses were harvested. BGC-823 gastric cancer cells were infected with the viruses. The protein expression of AKT1 was detected by Western blotting. The gastric cancer xenografts in nude mice were constructed using BGC-823 cells infected with the viruses, followed by the administration of doxorubicin. The size of tumor was evaluated and the growth curve of the tumor was drawn; HE staining was used to observe the pathological conditions of the xenografts; and the apoptosis of xenografts was examined by TUNEL assay. Results The recombinant plasmid of LV-shAKT1 was successfully constructed, and then transfected into HEK293T cells to produce high-titer lentivirus with a titer of 5×108 TU/mL. The expression of AKT1 protein in gastric cancer BGC-823 cells was significantly down-regulated after successfully infected with the LV-shAKT1. Nude mice xenografts experiment showed that AKT1 gene silencing inhibited the growth of tumor xenografts, and also enhanced the inhibitory effect of doxorubicin on the growth of tumor xenografts. TUNEL staining showed that AKT1 gene silencing promoted the apoptosis of tumor xenograft cells, and the effect was more obvious when combined with doxorubicin. Conclusion AKT1 gene silencing can enhance the sensitivity of gastric cancer xenografts to doxorubicin through promoting cell apoptosis.

Objective To investigate the effect of lapatinib on cell proliferation and apoptosis in acute myeloid leukemia HL60 cells in vitro and the related molecular mechanisms. Methods The HL60 cells were treated with 5, 10, 15 μmol/L lapatinib for 24 hours, and then morphological changes of the cells were observed under optical microscope. CCK-8 assay was used to assess the cell viability. Colony formation assay was performed to detect the cell proliferation ability. Cell apoptosis labeled by annexinV-FITC/PI were analyzed by flow cytometry. Wright modified LIU's staining and Hoechst33342 fluorescent staining were used to observe the morphology of the nucleus. Western blotting was utilized to detect the expressions of Bax, Bcl2, caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (cleaved PARP), cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A), c-MYC, AKT and p-AKT. Results Compared with the control group, lapatinib inhibited cell proliferation and promoted apoptosis, induced nuclear fragmentation, chromatin condensation of HL60 cells in a dose-dependent manner. Meanwhile, it down-regulated the expression of Bcl2, up-regulated the levels of Bax, cleaved caspase-3, cleaved caspase-9 and cleaved PARP, and decreased the levels of CIP2A, p-AKT and c-MYC. Conclusion Lapatinib could inhibit cell proliferation and promote apoptosis in HL60 cells by inhibiting the CIP2A/AKT/c-MYC signal pathway.

Objective To study the mechanism underlying the inhibitory effect of decursin on the apoptosis of rat renal tubular epithelial cells NRK-52E induced by cisplatin. Methods First, CCK-8 assay was used to detect the effects of 0, 10, 20, 40, 80, 100, 150, 200 μmol/L decursin and 0, 5, 10, 20, 30, 40, 50 μg/mL cispatin treatment for 24 hours on cell proliferation in NRK-52E cells via determining the half inhibitory concentration (IC50). Then, NRK-52E cells were stimulated with 20 μg/mL cisplatin combined with 10, 50, 100 μmol/L decursin, and cell activity was detected by CCK-8 assay. The cells were divided into normal control group, 20 μg/mL cisplatin stimulation group, and 10, 50, 100 μmol/L decursin treated groups. Cell morphological changes was observed under inverted microscope, morphological changes of nucleus was detected by DAPI staining, cell apoptosis was detected by flow cytometry, the level of intracellular ROS was detected by DCFH-DA staining, and the apoptosis marker proteins cleaved-caspase-3 and cleaved-PARP were examined by Western blot analysis. Results Compared with the normal control group, cisplatin significantly inhibited the activity of the cells, and IC50 was about 20 μg/mL; compared with the model group, in the decursin pretreatment groups, the level of intracellular ROS decreased remarkably, the expressions of cleaved-casspase-3 and cleaved-PARP proteins were reduced, and cell apoptosis was depressed. Conclusion Decursin can decrease the intracellular ROS level and inhibit the apoptosis of NRK-52E cells induced by cisplatin.

The development of new treatments beyond first-line in metastatic non-small cell lung cancer (NSCLC) contributed to the increase in overall survival. Metronomic chemotherapy involves several mechanisms of anti-tumor with less toxicity. Oral vinorelbine has paved the way for innovative treatment strategies through metronomic regimens. Therefore, this study assessed the efficacy and safety of metronomic oral vinorelbinen in advanced NSCLC after failure to multiple-lines treatments.

Objective: To investigate the clinical value of two-dimensional speckle tracking echocardiography(2D-STE) combined with high-sensitive cardiac troponin T (hs-cTnT) in early detection of the cardiotoxicity induced by chemotherapy drug. Methods: Seventy-five non-Hodgkin's lymphoma patients who received the CHOP regimen were recruited in this study. Conventional echocardiography and 2D-STE were performed on these patients before chemotherapy, the second day after the third course of chemotherapy (during chemotherapy) and the second day after the last course of chemotherapy (after chemotherapy). The parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (LS), global circumferential strain (CS) and global radial strain (RS). The serum hs-cTNT levels were tested simultaneously. Results: Three cycles of CHOP were completed in 30 patients and 6-8 cycles of CHOP were completed in 45 patients. The LVEF of 75 patients before, during and after chemotherapy was (63.8±2.6)%, (63.8±2.8)% and (64.0±3.3)%, respectively, without significant difference (P=0.91). However, the LS of 75 patients before, during and after chemotherapy was (-18.5±1.7)%, (-16.5±1.9)% and (-16.0±1.6)%, respectively. The CS was (-20.9±2.9)%, (-19.3±3.5)% and (-19.2±3.2)%, respectively. The RS was (39.2±6.4)%, (35.3±5.2)% and (35.0±6.2)%, respectively. The hs-cTnT was (0.001 0±0.002 0)ng/ml, (0.006 3±0.008 9)ng/ml and (0.007 3±0.003 8)ng/ml, respectively. The LS, CS and RS were significantly decreased while hs-cTnT was significantly increased during chemotherapy when compared to those before chemotherapy (all of P<0.01). Alternatively, the LS, CS, RS and hs-cTnT after chemotherapy were marginally different from those during chemotherapy (all of P>0.05). Moreover, T(LS-SD), T(CS-SD) and T(RS-SD) showed no significant difference before, during and after chemotherapy (all of P>0.05). The reduction of LS was positively associated with the enhancement of hs-cTnT after chemotherapy (r=0.60, P<0.01). Conclusion: 2D-STE combined with hs-cTnT can effectively and precisely detect the occult cardiotoxicity induced by anthracycline.

To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism.

To investigate the chemical compounds from the roots of Actinidia rufa, nine compounds were isolated by various column chromatography on silica gel and Sephadex LH-20, and high performance liquid chromatography (HPLC). Their structures were elucidated as 2α, 3β, 19α, 23, 24-pentahydroxyurs-12-en-28-oic acid-28-O-β-D-glucopyranoside (1), 2α, 3α, 19α, 24-tetrahydroxyurs-12-en-28-oic acid-28-O-β-D-glucopyranoside (2), 2α, 3α, 24-trihydroxyurs-12-en-28-oic acid (3), 2α, 3α, 24-trihydroxyolean-12-en-28-oic acid (4), 2α, 3α, 23, 24-tetrahydroxyurs -12-en-28-oic acid (5), 2α, 3β, 23, 24-tetrah-ydroxyurs-12-en-28-oic acid (6), 2α, 3β, 23-trihydroxy-12-en-28-oic acid (7), 2α, 3β, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (8), and 2α, 3α, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (9). Compounds 1 and 2 were isolated from the Actinidia genus for the first time. Compounds 2, 3, and 4 showed cytotoxic activity against human SKVO3 and TPC-1 cancer cell lines with IC₅₀ values ranging from 10.99 to 16.41 μmol•L⁻¹, compounds 3 and 4 have cytotoxic activity against human HeLa cancer cell line with IC₅₀ values of 15.53 and 13.07 μmol•L⁻¹, respectively.

Fourteen compounds were isolated from the 80% ethanol extract of Caragana stenophylla root, by using a combination of various chromatographic approaches, including silica gel sephadex LH-20 column chromatography, and preparative HPLC. On the basis of their physical and chemical properties and spectroscopic data, their structures were elucidated as 2-(4-hydroxy-3-methoxy lphenyl)-3-methoxyl benzofuran-6-ol (1), mucodianin C (2), isopterofuran (3), formononetin (4), afromosin (5), calycosin (6), acacetin (7), 3-O-methylkaempferol (8), liquiritigenin (9), isoliquiritigenin (10), variabilin (11), resveratrol (12), zhebeiresinol (13), and 2, 3-dicarboxy-6, 7-dihydroxy-1-(3', 4'-dihydroxy)-phenyl-1, 2-dihydronaphthalen (14). Compound 1 is a new benzofuran derivative, named as mucodianin S; compounds 2, 3, 11, 13, 14 were isolated from the genus Caragana for the first time, and compounds 4-10 were firstly isolated from Caragana stenophylla. MTT assay was used to determine their cytotoxicity of the isolated compounds against human tumor cell lines, and 2 showed cytotoxicity against human hepato cellular cancer (HepG2) and human cervical (HeLa) lines, with IC₅₀ values of (16.18±0.95), (3.75±0.08) μmol•L ⁻¹, respectively.

Objective To investigate the effects of verteporfin on the proliferation, invasion and migration of human breast cancer MDA-MB-231 cells and the underlying mechanism. Methods MDA-MB-231 cells in the logarithmic growth phase were randomly divided into control group and verteporfin treatment group. After MDA-MB-231 cells were treated with (0, 4, 8, 12, 16) μmol/mL verteporfin, the minimal inhibitory concentration was determined by CCK-8 assay. After treatment with 4 μmol/mL verteporfin, the invasion and migration abilities of MDA-MB-231 cells were detected by TranswellTM invasion assay and scratch wound healing assay, respectively. The expression levels of proliferation-associated proteins c-MYC, cyclin D1, Yes-associated protein (YAP), cysteine-rich protein 61 (CYR61) and connective tissue growth factor (CTGF) in MDA-MB-231 cells treated by (0, 4, 8, 12, 16) μmol/mL verteporfin were determined by Western blotting. Results Verteporfin markedly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner, and the minimal inhibitory concentration was 4 μmol/mL. The 4 μmol/mL verteporfin significantly inhibited the invasion and migration abilities of MDA-MB-231 cells. Verteporfin inhibited significantly the expressions of c-MYC, cyclin D1, YAP, CYR61 and CTGF. Conclusion Verteporfin significantly inhibits the proliferation, invasion and migration of MDA-MB-231 cells by down-regulating the expressions of YAP and its target genes CYR61 and CTGF.

The study was designed to investigate the anti-tumor and anti-angiogenic effects of alcohol extract from Euphorbia prostrata. The alcohol extract of E. prostrata was prepared, and the tolerated dosage was determined in mice by the test for acute toxicity. Then, MTT method was used to study the anti-proliferation effect of E. prostrata on normal cells and tumor cells. The rat aortic endothelial cells(RAECs) were primarily cultured. Subsequently, in vitro cell proliferation, migration and tubule formation assays were performed to detect the effect of alcohol extract of E. prostrata on proliferation, migration and angiogenesis. Western blot analysis was performed to detect the protein expressions of Akt, p-Akt, eNOS, p-eNOS, TGF-β1 and Smad3 in RAECs treated with E. prostrata. In addition, an in vivo transplanted hepatocellular carcinoma model in nude mice was established to detect nude mass, tumor volume and tumor weight. The contents of vascular endothelial growth factor(VEGF) and the platelet-derived growth factor-BB(PDGF-BB) in blood serum were detected by using ELISA kits. HE staining was performed to study the morphology of tumor tissues. The tolerated dosage of alcohol extract of E. prostrata in mice was 94.29 g•kg⁻¹. Alcohol extract of E. prostrata showed no inhibitory effect on L6 cells, but significantly inhibited the proliferations of HepG-2, PC12, A549, and Hela cells with the following order： HepG-2>Hela>PC12>A549. Meanwhile, alcohol extract of E. prostrata markedly inhibited the proliferation, migration and tube formation of RAECs, and enhanced the expressions of phosphorylated Akt and eNOS and increased the expressions of TGF-β1 and Smad3. In addition, E. prostrata notably inhibited the tumor growth in mice, and decreased the amount of VEGF, but increased the amount of PDGF-BB factor in serum of nude mice. The alcohol extract of E. prostrata may show an inhibitory effect on tumor growth and angiogenesis, which may contribute to its anti-tumor effect.

The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC₅₀ values ranging from 20.33 to 63.13 μmol•L⁻¹.