Abstract

Tumor drug resistance remains a major obstacle in the treatment of cancers. Increased DNA repair is a primary mechanism of acquired resistance to platinum chemotherapy. TP53, Chk2 and ERCC1 of the DNA damage/repair pathway were activated after cells were exposed to cisplatin or dicycloplatin. Overexpression of p53 in wt-p53 (but not p53-deficient) cells doubled Chk2 phosphorylation. p53 knockdown greatly reduced Chk2 phosphorylation, indicating that wild type p53, in response to platinum-drugs, plays a role in the upstream regulation of the DNA-adduct repair pathway and mediates acquired platinum resistance. We strongly suggest that it is important to include p53 mutational status in any p53-involved studies due to the functional differentiation of wt-p53 and p53-mutant.