1. Inhibition of Snail Family Transcriptional Repressor 2 (SNAI2) Enhances Multidrug Resistance of Hepatocellular Carcinoma Cells
- Author
-
Lei Huang, Lei Li, Ke-Wen Zhao, Yaping Lv, Xiao-Bo Wang, Guo-Qiang Chen, Wei Jin, Rong-Jie Fu, Xin-Yu Zhao, and Chao Meng
- Subjects
0301 basic medicine ,Transcription, Genetic ,Carcinogenesis ,Molecular biology ,Cancer Treatment ,Gene Expression ,lcsh:Medicine ,ATP-binding cassette transporter ,Mice ,Animal Cells ,Cancer Stem Cells ,Medicine and Health Sciences ,Neoplasm Metastasis ,RNA, Small Interfering ,lcsh:Science ,Multidisciplinary ,Pharmaceutics ,Liver Diseases ,Stem Cells ,Liver Neoplasms ,Drug Resistance, Multiple ,Up-Regulation ,Oncology ,Optical Equipment ,Neoplastic Stem Cells ,Engineering and Technology ,Female ,Efflux ,Cellular Types ,Liver cancer ,Research Article ,Clinical Oncology ,Carcinoma, Hepatocellular ,Epithelial-Mesenchymal Transition ,DNA transcription ,Equipment ,Gastroenterology and Hepatology ,Biology ,DNA construction ,Carcinomas ,03 medical and health sciences ,Drug Therapy ,Cell Line, Tumor ,Gastrointestinal Tumors ,medicine ,Genetics ,Gene silencing ,Chemotherapy ,Animals ,Humans ,Epithelial–mesenchymal transition ,Gene Silencing ,Transcription factor ,Cell Proliferation ,lcsh:R ,Cancer ,Cancers and Neoplasms ,Biology and Life Sciences ,Prisms ,Hepatocellular Carcinoma ,Cell Biology ,medicine.disease ,Research and analysis methods ,SNAI2 ,030104 developmental biology ,Molecular biology techniques ,Verapamil ,Plasmid Construction ,Cancer research ,ATP-Binding Cassette Transporters ,lcsh:Q ,Snail Family Transcription Factors ,Clinical Medicine - Abstract
China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells. Suppression of SNAI2 suffices to up-regulate several cancer stem genes. Although unrelated to the metastatic ability, SNAI2 inhibition does increase the efflux of Hoechst 33342 and enhance multidrug resistance in vitro and in vivo. In agreement with this data, we demonstrate for the first time that decreasing SNAI2 level can transcriptionally upregulate several ATP binding cassette (ABC) transporter genes such as ABCB1. Moreover, ABC transporters' inhibitor verapamil can rescue the multidrug resistance induced by SNAI2 inhibition. Our results implicate that SNAI2 behaves as a tumor suppressor by inhibiting multidrug resistance via suppressing ABC transporter genes in HCC cells.
- Published
- 2016