Abstract: Objective:To explore the inhibitory effects of gomisin A (GA) in combination with carboplatin (CBP)on the proliferation,invasion and metastasis of human ovarian cancer Skov3 cells and their mechanisms,and to illustrate the synergistic antitumor effect of GA. Methods: The ovarian cancer Skov3 cells were treated with different concentrations of GA combined with different concentrations of CBP.MTT assay was used to detect the inhibitory rates of proliferation.According to the results,the appropriate concentrations of GA and CBP were conformed.The Skov3 cells were treated with PBS,GA(0.04 μmol·L^-1),CBP (16 mg·L^-1) and GA (0.04 μmol·L^-1) in combination with CBP (16 mg·L^-1),respectively, and used as control group,GA group,CBP group and GA+CBP group. After 48 h of treatment,the cell morphology was observed by optical microscope,the cell reproductive ability was determined by clonogenic cell survival assay,and the cell migration ability was measured by cell wound healing test;Transwell experiment was used to detect the cell invasion ability.The expression levels of MMP-2 and MMP-9 mRNA were determined by RT-PCR and the protein expression levels of MMP-2,MMP-9,AKT1 and pAKT1 were determined by Western blotting method. Results: Compared with GA and CBP groups,the inhibitory rate of proliferation of Skov3 cells in GA + CBP group was significantly increased(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. The results of clone formation assay showed that the colony formation rates in CBP and GA+CBP groups were decreased compared with control group(P<0.05 or P<0.01);the colony formation rate of cells in GA + CBP group was significantly decreased compared with GA and CBP groups(P<0.01); the wound scratch assay results suggested that the number of metastic Skov3 cells in GA and CBP groups were decreased compared with control group;and the number of metastic Skov3 cells in GA + CBP group was decreased compared with GA and CBP groups.The results of Transwell expriment showed that the capacities of cells passing the ECM in GA and CBP groups were decreased compared with control group;the capacity of cells passing the ECM was decreased compared with GA and CBP groups.The RT-PCR and Western blotting results showed that the expression levels of MMP-2 and MMP-9 mRNA in GA+CBP group were down-regulated compared with GA and CBP groups(P<0.01),and the expression levels of MMP-2,MMP-9,AKT1 and pAKT1 protein were down-regulated(P<0.01). Conclusion: GA can enhance the ability of CBP to inhibit the proliferation,invasion and metastasis of human ovarian cancer Skov3 cells,and thus play a role in decreasing the toxicity and increasing the efficacy of chemotherapy.

Key words: carboplatin, invasion and metastasis, ovarian neoplasms, gomisin A, cell proliferation