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

// Tengyue Zhang 1, 2, * , Kelong Ma 3, * , Jin Huang 2, * , Shitang Wang 4, * , Yabei Liu 2 , Gaofei Fan 2 , Miao Liu 2 , Guangshan Yang 2 , Cheng Wang 4 and Pingsheng Fan 1, 2 1 School of Clinical Medicine, Shan Dong University, Jinan 250100, China 2 The Cancer Hospital of Anhui Province, Provincial Hospital of Anhui Medical University, Hefei 230032, China 3 Clinical College of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230032, China 4 Department of General Surgery, Provincial Hospital of Anhui Medical University, Hefei 230032, China * These authors have contributed equally to this work Correspondence to: Pingsheng Fan, email: wangal2014@sohu.com Cheng Wang, email: blackpippy@163.com Keywords: hepatocellular carcinoma (HCC); verapamil (VER); doxorubicin (ADM); CDKN2B; chemotherapy resistance Received: June 14, 2017      Accepted: October 05, 2017      Published: October 26, 2017 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.