Enhancing radiosensitivity of TE1, TE8, and TE 11 esophageal squamous carcinoma cell lines by Hdm2-siRNA targeted gene therapy in vitro.

Abstract

Introduction: Human double minute2 (hdm2) level increases in most human malignancies. Therefore, inhibition of tumor growth and also induction of radiosensitivity may be provided by hdm2 inhibitors. The effects of hdm2-siRNA on hdm2 protein expression, cell apoptosis rate, and radiosensitivity of human esophageal squamous cell carcinoma (ESCC) were studied. Methods: The hdm2 gene was silenced in TE1, TE8, and TE11 ESCC cell lines using 200nM siRNA by liposomal transfection method followed by irradiation with 0.5, 1, 2, 4, and 6 Gy γ-rays in vitro. The gene expression levels were evaluated by real time PCR and Western Blotting methods. MTT, TUNEL, and also colony forming assays were used to compare the radiosensitivity of the cell lines before and after the treatments. Results: Hdm2-siRNA reduced the hdm2 protein as compared to the vehicle control and scrambled groups, and also increased the radiation-induced apoptosis especially in TE11 cells. The related dose reduction factors (DRFs) for the silenced TE1, TE8, and TE11 cells calculated to be 1.20, 1.30, and 2.75, respectively. Conclusion: Increasing radiosensitivity of tumor cells may be provided by silencing the oncogenes.