Abstract: Objective: To explore the effect of gomisin A (GA) in combination with carboplatin (CBP)on the apoptosis of ovarian cancer Skov3 cells,and to illustrate the synergistic antitumor effect of GA. Methods: The ovarian cancer Skov3 cells were treated with GA combined with CBP.MTT assay was used to detectthe inhibitory rates of proliferation and the appropriate concentrations of GA and CBP were selected according to the results.The Skov3 cells were divided into control group,GA (0.04 μmol·L^-1) group,CBP (16 mg·L^-1)group and GA(0.04 μmol·L^-1)+CBP(16 mg·L^-1) group. After 48 h treatment,the cell morphology was observed by microscope,the apoptotic rate was measured by flow cytometry, the apoptotic index(AI) was observed by TUNEL staining,the mitochondrial membrane potential was detected by JC-1 staining,and the mRNA and protein expression levels of apoptosis-related genes (Bax,caspase-3,Stat3) were determined by RT-PCR and Western blotting method. Results: The inhibitory rate of proliferation of Skov3 cells in GA + CBP group(52.1%) was significantly higher than those in GA and CBP groups(P<0.01).The concentrations of GA and CBP for the best dose ratio were 0.04 μmol·L^-1 and 16 mg·L^-1,respectively. Compared with control group,the cell refractivities were decreased,the cells retracted,and part of cells were suspended in GA group and CBP groups;there were more suspended cells and cell retraction phenomenon was more prominent in GA + CBP group.The results of TUNEL staining and flow cytometry showed that the AI and apoptotic rate of cells in GA + CBP group were significantly increased compared with control group,GA and CBP group(P<0.05 or P<0.01);the JC-1 staining results suggested that the mitochondrial membrane potential of Skov3 cells in GA + CBP group was decreased(P<0.05 or P<0.01).The RT-PCR and Western blotting results showed that the expression levels of Bax and caspase-3 mRNA and protein were up-regulated(P<0.05) and the expression levels of Bcl-2 and Stat3 mRNA and protein in GA + CBP group were down-regulated compared with control,GA and CBP groups(P<0.05). Conclusion: GA can enhance the ability of CBP to induce the apoptosis of human ovarian cancer Skov3 cells,and its mechanisms may be related to the up-regulation of the Bax and Caspase-3 expressions and the down-reguation of the Bcl-2 expression;GA can synergize the induction of CBP on apoptosis.

Key words: gomisin A, apoptosis, ovarian neoplasms, carboplatin