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    Oleuropein reduces cisplatin resistance in ovarian cancer by targeting apoptotic pathway regulators. Hashemi Sheikhshabani Somayeh,Amini-Farsani Zeinab,Rahmati Shima,Jazaeri Ali,Mohammadi-Samani Marzieh,Asgharzade Samira Life sciences AIMS:Despite many attempts to treat ovarian cancer, 13,940 individuals perish annually due to this disease worldwide. Chemotherapy is the main approach to ovarian cancer treatment, but the development of drug resistance is a major obstacle to the successful treatment. Oleuropein is a phenolic ingredient with anticancer characteristics. This study was aimed at investigating the effect of oleuropein on cell viability, cisplatin resistance, and apoptosis, as well as the expression levels of miR-34a, miR-125b, miR16, miR-21, and some of their potential target genes in ovarian cancer cells. MAIN METHODS:A2780S and A2780/CP cell lines were exposed to different concentrations of oleuropein alone or in combination with cisplatin for 48 h and 72 h. After that, the cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. Bioinformatics analyses were conducted using STRING database and Cytoscape software. The effect of oleuropein and/or cisplatin on the expression of miRNAs and target genes was assessed via Real-time PCR. KEY FINDINGS:Upon treatment with oleuropein, the expression of P21, P53, and TNFRSF10B increased while that of Bcl-2 and Mcl1 decreased. Moreover, this is the 1st report of a significant decrease in the expression of miR-21 and increase in the expression of miR-34a, miR-125b, and miR16 by oleuropein and/or cisplatin in ovarian cancer cells. SIGNIFICANCE:Altogether, these data revealed that oleuropein regulated the expression of the above-mentioned miRNAs in ovarian cancer cells, which potentially resulted in apoptosis induction, cell proliferation inhibition, and cisplatin resistance decline in ovarian cancer cells. To confirm the results of this study, it is suggested that similar experiments be performed in animal models of ovarian cancer. 10.1016/j.lfs.2021.119525