Apoptosis Induction With Combined Use of Cisplatin and Fisetin in Cisplatin-Resistant Ovarian Cancer Cells (A2780)

Background: ovarian cancer is the leading cause of death caused by genital cancers.one of the most common treatments for this type of cancer is chemotherapy by cisplatin,which induces apoptosis in cancer cells. apoptosis is a type of physiological celldeath. cisplatin chemotherapy usually has several side effects and cellular resistanceto cisplatin is a common incidence. in order to overcome these problems, the use ofcombination therapies using natural substances has been considered. fisetin is a flavonoidwith anti-cancer activity which induces apoptosis .in this study, the apoptosisinduced by cisplatin along with fisetin in cisplatin-resistant ovarian cancer cell line(a2780) was investigated.methods: in the present experimental study, the effect of combined use of fisetin andcisplatin on ovarian cancer cell lines (a2780) was investigated by using mtt assay.cell death was also determined by dapi, acridine orange/propidium iodide, and annexin/pi assay. apoptotic gene expression of bax, bcl-2, caspase 3, and caspase 9 wasalso assessed by real time pcr.results: the results of mtt assay indicated that the combined treatment of fisetinand cisplatin effectively inhibits proliferation of a2780 cells. the results of dapi stainingshowed that fragmentation of chromatin in cells occurred in the combined treatment.acridine orange-propidium iodide staining and annexin/pi staining showed anincrease in the rate of apoptotic cells in cells under combined treatment. the results ofthe study regarding changes in gene expression also indicated that bax pro-apoptoticgene expression and bcl-2 anti-apoptotic gene expression increased in cells undertreatment; moreover, gene expression of caspases 3 and 9 significantly increased aswell.conclusion: according to the findings of this study, the combined use of cisplatin andfisetin increases the induction of apoptosis in cisplatin-resistant ovarian cancer cells(a2780); therefore, the combined use of cisplatin and fisetin can be considered apromising strategy in the treatment of ovarian cancer.