Role of the p53 and PI3K pathways in drug response of mouse ovarian epithelial cells in vitro
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The aim of the study was to investigate the role of the p53 and PI3K pathway in drug response of mouse ovarian epithelial cells in vitro. Ovarian cancer is the fifth-leading cause of cancer death among women and is the most lethal gynaecological cancer. Different genetic and epigenetic abnormalities have been detected in ovarian cancers. Ovarian tumors can be divided in three types: (1) Surface epithelial-stromal tumor (2) Sex-cord stromal tumor (3) Germ cell tumor. Epithelial ovarian cancers can either be divided further into histotypes or molecular classification. Mouse ovarian epithelial cells, ID8, were used to analyse drug response of FL118, Topotecan and Carboplatin. FL118, a recently identified novel drug, that has shown to be a powerful antitumor drug and specifically targets anti-apoptotic proteins including XIAP, cIAP2, Mcl-1, and Survivin. Mutant p53 (R175H and R273H) expression is undetectable in transfected ID8 cells but can be rescued by proteasome inhibitor MG132. ID8 transfected cells with mutants BRAF V600E and PIK3CA showed activation of the PI3K pathway. ID8 cells with p53R273H have a slightly higher IC50 for FL118 and Topotecan compared with the other p53 mutants and the control cell line. However, more research has to be done on the effect of FL118 on DNA repair.