The therapeutic potential of survivin promoter-driven siRNA on suppressing tumor growth and enhancing radiosensitivity of human cervical carcinoma cells via downregulating hTERT gene expression

Abstract

Human telomerase is a ribonucleoprotein complex composed of two subunits, an RNA component (hTR) and a human telomerase reverse transcriptase component (hTERT). The activation of telomerase, a process regulated by the human telomerase reverse transcriptase (hTERT), is a crucial step during cellular immortalization and malignant transformation. hTERT is overexpressed in most malignant cells but undetectable in most normal somatic cells. To explore its possibility as a therapeutic target for human cervical carcinoma, we developed a novel tumor-specific RNA interference system targeting hTERT by using the survivin promoter and investigated the effects of it on the proliferation, apoptosis and radiosensitivity in human cervical carcinoma cells (HeLa). The treatment of HeLa cells by hTERT gene RNAi not only could inhibit the proliferation of human cervical carcinoma cells (HeLa), but also could enhance the radiosensitivity of those cells via downregulation of their mRNA and protein expression. Therefore, survivin promoter-driven siRNA expression vector targeting hTERT may have potential use in radiosensitization therapy with targeted tumor gene silencing effect in human cervical carcinomas. ©2007 Landes Bioscience.