title: Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.
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.
authors.affiliation: Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Geling
authors.initials: G
authors.lastname: Teng
authors.affiliation: Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Ju
authors.affiliation: Department of Radiation Medicine, Peking University Health Science Centre, Beijing 100191, P.R. China.
authors.forename: Yepeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Chest Hospital, Jinan, Shandong 250013, P.R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Respiratory Medicine, Chest Hospital, Jinan, Shandong 250013, P.R. China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chi
authors.affiliation: Foreign Language Department, Shandong Medical College, Jinan, Shandong 250002, P.R. China.
authors.forename: Xiuan
authors.initials: X
authors.lastname: Mu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D001388:Aziridines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D041722:Genes, Transgenic, Suicide; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009601:Nitroreductases / Q000235:genetics* / Q000378:metabolism; D011355:Prodrugs; D011836:Radiation Tolerance / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D011355:Prodrugs; C100099:tretazicar; D009601:Nitroreductases