Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

摘要: A large fraction of human tumours carries mutations in the p53 gene. plays a central role controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack function impairs these cellular processes, this may be basis resistance to chemotherapeutic regimens. By virtue involvement mismatch repair modulating cytotoxic pathways response damaging agents, we investigated effects loss Pms2 on sensitivity panel widely used anticancer agents E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient Pms2. We report that lack gene is associated with an increased sensitivity, ranging from 2–6-fold, some types including topoisomerase II poisons doxorubicin, etoposide mitoxantrone, platinum compounds cisplatin oxaliplatin, taxanes docetaxel paclitaxel, antimetabolite gemcitabine. In contrast, no change was found after treatment 5-fluorouracil. Cell analysis revealed both, Pms2-deficient -proficient cells, retain ability arrest at G2/M treatment. The data indicate concomitant chemosensitises p53-deficient cells positively modulates survival by mechanisms independent p53, cytotoxicity paralleled apoptosis. Tumour-targeted functional inhibition valuable strategy for increasing efficacy p53-mutant cancers.