ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA

作者：Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma · 发表于：Oncotarget · 年份：2014 · DOI：10.18632/oncotarget.2832 · 被引用次数：40 · 研究领域：Cancer-related gene regulation、Drug Transport and Resistance Mechanisms、Cancer Mechanisms and Therapy

// Hongxin Ma 1,* , Xuetian Yue 1,* , Lifen Gao 1 , Xiaohong Liang 1 , Wenjiang Yan 1 , Zhenyu Zhang 1 , Haixia Shan 1 , Hualin Zhang 1 , Brett T. Spear 2 and Chunhong Ma 1 1 Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, P.R. China 2 Department of Microbiology, Immunology & Molecular Genetics and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA * These authors contributed equally to the work Correspondence: Chunhong Ma, email: // Keywords : ZHX2, transcriptional repression, chemoresistance, p-glycoprotein, apoptosis Received : September 23, 2014 Accepted : November 25, 2014 Published : November 26, 2014 Abstract We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated suppression of...