RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity

Zhang,Wenxuan; Xing,Lina

doi:10.3892/ijo.2013.2051

RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity

Authors:
- Wenxuan Zhang
- Lina Xing
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Affiliations: Department of Radiation Oncology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, P.R. China
Published online on: August 6, 2013 https://doi.org/10.3892/ijo.2013.2051
Pages: 1228-1234

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Abstract

Telomerase activity (TA) is reactivated in more than 90% of all human malignant tumors and normal somatic cells that lack TA. Thus, human TERT (hTERT) is a promising target in malignant tumor treatment. RNA interference is a powerful tool for gene silencing. In this study, we constructed siRNA#1-4 to knock down hTERT. All siRNAs were able to downregulate hTERT differently and we chose siRNA#3 (most effectively) in the following experiments. We studied the effects on cell proliferation, cell cycle, cell apoptosis and radiosensitivity using SiHa cells. Our results showed that siRNA#3 was able to silence hTERT gene effectively. The silencing of hTERT could induce immediate growth arrest, enhance the S phase in cell cycle study and lead to early apoptosis in human cervical cancer cells (SiHa). In clonogenic assays, we used multitarget-single hit and linear-quadratic models to assess the radiosensitivity after knockdown of hTERT. All results of parameters (D0, Dq, α, β) indicated that downregulation of hTERT enhanced radiosensitivity in SiHa cells.

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