RIPK1 Inhibition Enhances Pirarubicin Cytotoxic Efficacy through AKT-P21-dependent Pathway in Hepatocellular Carcinoma.

ABSTRACT: Pirarubicin (THP) is a new generation cell cycle nonspecific anthracycline anticancer drug. Pirarubicin and pirarubicin-based combination therapies have been demonstrated to be effective against HCC in TACE. However, the drug resistance limits its therapeutic efficacy. Receptor-interacting protein kinase 1 (RIPK1) displays a critical role in cell death. Here we found that RIPK1 and p21 may participate in the resistance to pirarubicin. In this study, we first found that inhibition of RIPK1 significantly decreased pAKT and increased p21, accompanied by G0/G1 phase cell cycle arrest and cell anti-proliferation in pirarubicin-treated hepatocellular carcinoma cells. Moreover, phosphorylation of AKT reversed the anti-proliferative effect of RIPK1 inhibitor in HCC, which proved that RIPK1-AKT-P21

SUBMITTER: Huang H 

PROVIDER: S-EPMC6299408 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature