The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line.

Abstract

Drug resistance to cisplatin with continuous drug treatment is one of the most common causes of chemotherapy failure in hepatic carcinoma. Accumulating evidence suggests that WEE1 G2 checkpoint kinase (WEE1) is involved in cisplatin resistance, which has been demonstrated to correlate with cancer initiation and progression. However, the role and molecular mechanism of WEE1 in the drug resistance of hepatic cancer remains unclear. In the present study, using the WEE-knockdown hepatic cancer cell line HepG2/DDP, the role of WEE1 and its molecular mechanism were investigated. It was demonstrated that silencing WEE1 expression resulted in an increased cisplatin sensitivity of HepG2/DDP, in addition to an increased rate of apoptosis and intracellular concentration of rhodamine 123. The expression levels of P-gp, MDR1, MRP1, LRP, BCL-2, survivin and GST in WEE1-silenced HepG2/DDP cells were significantly reduced, and phosphorylation levels of MEK and ERK were significantly downregulated. The results demonstrated that WEE1 negatively regulated the multidrug resistance potential of human hepatic cancer cells by modulating the expression of relevant drug resistance genes and the activity of the MEK/ERK pathway. Therefore, WEE1 may be a monitoring bio-marker for drug resistance, and a therapeutic target in hepatic cancer.