Reference - Detail
|Author||Sanada Y, Sasanuma H, Takeda S, Tano K, Masunaga SI.|
|Title||Disruption of Hif-1α enhances cytotoxic effects of metformin in murine squamous cell carcinoma.|
|Journal||Int. J. Radiat. Biol.|
PURPOSE:In the present study, we investigated whether the disruption of the Hif-1α gene affects the sensitivity of SCC VII cells to metformin and also if metformin functions as a radiosensitizer using murine squamous cell carcinoma (SCC VII) cells.
MATERIALS AND METHODS:Cultured SCC VII and SCC VII Hif-1α-deficient cells were incubated with metformin under glucose-free and/or hypoxia-mimetic conditions and cell viabilities were measured. Tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating cells. Tumor-bearing mice were then subjected to γ-ray irradiation after the metformin treatment. Immediately after irradiation, cells were isolated from some tumors and incubated with a cytokinesis blocker. The responses of quiescent and total (= proliferating + quiescent) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU.
RESULTS:The disruption of Hif-1α increased the sensitivity of SCC VII cells to metformin in glucose-free medium. Metformin-induced decreases in the percentage of dead cells in the presence of CoCl2 were partially reduced when Hif-1α was disrupted. In vivo, metformin increased the radiosensitivity of SCC VII Hif-1α-deficient cells.
CONCLUSION:The combination of disruption of Hif-1α and metformin effectively enhanced the radiosensitivity of SCC VII cells.
|MeSH||Animals Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Survival / drug effects Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / physiology* Metformin / pharmacology* Mice Mice, Inbred C3H|
|Prokaryotes E. coli|