Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

Teng,Geling; Ju,Yuanrong; Yang,Yepeng; Hua,Hu; Chi,Jingyu; Mu,Xiuan

doi:10.3892/mmr.2016.5917

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

Authors:
- Geling Teng
- Yuanrong Ju
- Yepeng Yang
- Hu Hua
- Jingyu Chi
- Xiuan Mu
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Affiliations: Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong 250021, P.R. China, Department of Radiation Medicine, Peking University Health Science Centre, Beijing 100191, P.R. China, Department of Respiratory Medicine, Chest Hospital, Jinan, Shandong 250013, P.R. China, Foreign Language Department, Shandong Medical College, Jinan, Shandong 250002, P.R. China
Published online on: November 1, 2016 https://doi.org/10.3892/mmr.2016.5917
Pages: 5164-5170
Copyright: © Teng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

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