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Inhibition of Snail Family Transcriptional Repressor 2 (SNAI2) Enhances Multidrug Resistance of Hepatocellular Carcinoma Cells.
- Source :
-
PloS one [PLoS One] 2016 Oct 19; Vol. 11 (10), pp. e0164752. Date of Electronic Publication: 2016 Oct 19 (Print Publication: 2016). - Publication Year :
- 2016
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- ATP-Binding Cassette Transporters antagonists & inhibitors
ATP-Binding Cassette Transporters genetics
Animals
Cell Line, Tumor
Cell Proliferation drug effects
Cell Proliferation genetics
Drug Resistance, Multiple drug effects
Epithelial-Mesenchymal Transition drug effects
Epithelial-Mesenchymal Transition genetics
Female
Gene Silencing
Humans
Mice
Neoplasm Metastasis
Neoplastic Stem Cells drug effects
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
RNA, Small Interfering genetics
Transcription, Genetic drug effects
Transcription, Genetic genetics
Up-Regulation drug effects
Up-Regulation genetics
Verapamil pharmacology
Carcinoma, Hepatocellular pathology
Drug Resistance, Multiple genetics
Liver Neoplasms pathology
Snail Family Transcription Factors deficiency
Snail Family Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27760172
- Full Text :
- https://doi.org/10.1371/journal.pone.0164752