Study On The Antitumor Effect Of Metformin Combined With Carboplatin On Ovarian Cancer SKOV3 Cells In Vitro

Objective:to study the antitumor effect of metformin combined with carboplatin on ovarian cancer SKOV3 cells in vitro,and to explore the synergistic effect of metformin on carboplatin and its mechanismMethods:Ovarian cancer SKOV3 cells were routinely resuscitated and cultured in vitro.ovarian cancer SKOV3 cells were treated with different concentrations of metformin and carboplatin alone or in combination with their effective concentrations(i.e.,divided into blank control group,metformin group,carboplatin group and metformin combined with carboplatin group).The morphological changes of-each group were observed under microscope.MTT reduction assay was used to detect the cell proliferation inhibition rate after 24,48 and 72 hours.Annexin V/PI staining and flow cytometry were used to detect the apoptosis rates in each groupThe expressions of survivin zRNA and PARP-1 mRNA in each group were detected by RT-PCR4.Results:1.Ovarian cancer SKOV3 cells are adherent growth cells.After the effect of drugs,the cell morphology changes,the number of heteromorphic cells increases,more particles appear in the cytoplasm,and the number of cell fragments in the culture medium increases.2.the results suggest detennined by MTT method and compared with the blank control group,treated with metformin alone or carboplatin of SKOV3 cell body showed obvious growth inhibition(P<0.05),and the concentration and time dependence,whereas metformin and carboplatin combined application can enhance the inhibitory effect,compared with the other three groups differences were statistically significant(P<0.05).3.Flow cytometry results showed that after 48 hours of metformin or carboplatin alone,the apoptosis rate of SKOV3 cells was significantly higher than that of the blank control group(P<0.05).After 48 hours of combined metformin and carboplatin,the apoptosis rate of SKOV3 cells was significantly higher than that of the other three groups(P<0.05).4.Rt-pcr showed that compared with the blank control group,survivin mRNA and parp-1 mRNA expression levels of SKOV3 cells treated with metformin or carboplatin alone were significantly decreased(P<0.05),Compared with the other three groups,survivin mRNA and parp-1 mRNA expression levels of SKOV3 cells treated with metformin and carboplatin were significantly decreased(P<0.05).Conclusion:1.Metformin can inhibit the proliferation ot ovarian cancer SKOV3 cells with a time-dose effect;2.Metformin inhibits the proliferation of ovarian cancer SKOV3 cells by inducing apoptosis.3.Metformin can increase the sensitivity of ovarian cancer SKOV3 cells to platinum-based chemotherapy drugs,and the two have a synergistic effect.4.The mechanism of metformin in enhancing the sensitivity of platinum chemotherapy drugs may be related to its inhibition of survivin and PARP-1 expression.