REGULATORY MECHANISM OF DUSP16 IN CANCER RESISTANCE TO PLATINUM-BASED THERAPIES

Abstract

Platinum-based chemotherapeutic agents remain the backbone of treatment for various solid tumours, and resistance to platinum-based therapies is the main limitation. In this study, the role DUSP16/MKP7 in cancer resistance to chemotherapy drugs was investigated. We observed that higher expression of DUSP16 in breast, colorectal, nasal pharyngeal, and gastric cancer cells correspond to increased resistance to chemotherapy induced apoptosis. Chemo drugs activate JNK and p38 leading to phosphorylation and activation of Bax, a pro-apoptotic member of the Bcl-2 protein family. Activated Bax translocate to mitochondria to trigger caspase 9/3 apoptosis. We showed that inhibition or knocking out of Bax in DUSP16-overexpression cells abrogated DUSP16-mediated chemoresistance. In conclusion, this study demonstrated that DUSP16 expression in cancer cells inhibits p38/JNK-mediated Bax activation, thereby preventing mitochondria-mediated apoptosis induced by chemo drug treatment. DUSP16 could be a biomarker for efficacy of various chemotherapy drug treatment.