CDKN2B is critical for verapamil-mediated reversal of doxorubicin resistance in hepatocellular carcinoma.

Tengyue Zhang,Gaofei Fan,Pingsheng Fan,Jin Huang,Kelong Ma,Guangshan Yang,Yabei Liu,Cheng Wang,Shitang Wang,Miao Liu

doi:10.18632/oncotarget.22123

Abstract

In this study, we explored the function and mechanism of CDKN2B genes in verapamil (VER)-induced reversal of resistance to doxorubicin (ADM) chemotherapy in hepatocellular carcinoma (HCC). We examined 4 HCC cell lines and found that the expression levels of CDKN2B genes correlated with the level of apoptosis induced by ADM+VER. Overexpression of CDKN2B genes promoted apoptosis in cells treated with VER+ADM. CDKN2B knockdown using siRNA weakened the effect of ADM+VER, indicating that ADM+VER promotes HCC cell apoptosis and that CDKN2B genes participate in VER-mediated promotion in tumor cell apoptosis. Future research will further explore the functional mechanism, and the associated signal transduction pathways via which CDKN2B affects HCC drug resistance.

Highlights

hepatocellular carcinoma (HCC) is a common substantive tumor in China and the second most malignant tumor in terms of fatality rate and threat to public health [1]
We examined 4 HCC cell lines and found that the expression levels of CDKN2B genes correlated with the level of apoptosis induced by ADM+VER
CDKN2B knockdown using siRNA weakened the effect of ADM+VER, indicating that ADM+VER promotes HCC cell apoptosis and that CDKN2B genes participate in VER-mediated promotion in tumor cell apoptosis

Summary

Introduction

HCC is a common substantive tumor in China and the second most malignant tumor in terms of fatality rate and threat to public health [1]. Most patients are diagnosed in the middle and terminal stages after the optimal surgical opportunity has passed because of the long latency and quick development of HCC. Transcatheter arterial chemoembolization (TACE) is an important therapy for these middle and terminal stage HCC patients [2]. Chemotherapy and targeted drugs are the main means to prolong the survival time of HCC patients, but their therapeutic effect is limited by drug resistance. Approximately 50% of current HCC responds to standard chemotherapy and sorafenib, which is the most effective targeted drug. Even among these responders, the survival time is only prolonged by 3 months, based on the systematic analysis of multiple random clinical control test results [3, 4]

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Results

Conclusion