Silencing of the hTERT gene by shRNA inhibits colon cancer SW480 cell growth in vitro and in vivo

Ai-Qun Liu; Lian-Ying Ge; Xiao-Ling Lu; Xiao-Ling Luo; Yan-Ling Cai; Xing-Qing Ye; Fang-Fang Geng

doi:10.1371/journal.pone.0107019

Silencing of the hTERT gene by shRNA inhibits colon cancer SW480 cell growth in vitro and in vivo

PLoS One. 2014 Sep 10;9(9):e107019. doi: 10.1371/journal.pone.0107019. eCollection 2014.

Authors

Ai-Qun Liu¹, Lian-Ying Ge¹, Xiao-Ling Lu², Xiao-Ling Luo³, Yan-Ling Cai¹, Xing-Qing Ye⁴, Fang-Fang Geng¹

Affiliations

¹ Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China.
² National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi, P.R. China.
³ Science and Technology Agency, Guangxi Medical University, Nanning, Guangxi, P.R. China.
⁴ Department of Pathology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China.

Abstract

Human telomerase reverse transcriptase (hTERT) is the key enzyme responsible for synthesizing and maintaining the telomeres on the ends of chromosomes, and it is essential for cell proliferation. This has made hTERT a focus of oncology research and an attractive target for anticancer drug development. In this study, we designed a small interfering RNA (siRNA) targeting the catalytic subunit of hTERT and tested its effects on the growth of telomerase-positive human colon carcinoma SW480 cells in vitro, as well as on the tumorigenicity of these cells in nude mice. Transient and stable transfection of hTERT siRNA into colon cancer SW480 cells suppressed hTERT expression, reduced telomerase activity and inhibited cell growth and proliferation. Knocking down hTERT expression in SW480 tumors xenografted into nude mice significantly slowed tumor growth and promoted tumor cell apoptosis. Our results suggest that hTERT is involved in carcinogenesis of human colon carcinoma, and they highlight the therapeutic potential of a hTERT knock-down approach.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / genetics
Carcinoma / enzymology
Carcinoma / genetics
Carcinoma / pathology
Carcinoma / therapy*
Cell Line, Tumor
Cell Proliferation
Colonic Neoplasms / enzymology
Colonic Neoplasms / genetics
Colonic Neoplasms / pathology
Colonic Neoplasms / therapy*
Gene Expression Regulation, Neoplastic*
Genetic Therapy / methods
Humans
Mice
Mice, Nude
Neoplasm Transplantation
RNA, Small Interfering / genetics*
RNA, Small Interfering / metabolism
Telomerase / antagonists & inhibitors*
Telomerase / genetics
Telomerase / metabolism
Telomere Homeostasis

Substances

RNA, Small Interfering
TERT protein, human
Telomerase

Grants and funding

This study was supported by the Natural Science Foundation of Guangxi (grant 2010GXNSF013238, http://www.gxst.gov.cn/zwgk/kjxmgl/xmxdgg/600619_7.shtml) and the Programs for Changjiang Scholars and Innovative Research Teams at University (No. IRT1119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.