Effect of BMI-1 on radiosensitization of esophageal carcinoma cells after silencing of BMI-1 gene

Objective: To investigate the effects of BMI-1 expression inhibition by RNA interference on the radiosensitivity of esophageal cancer TE-13 cells and its mechanism. Methods: The siRNA based on the sequence of BMI-1 mRNA was synthesized to transfect cultured TE-13 cells as BMI-1 siRNA group, a negative one was synthesized to transfect cultured TE-13 cells as negative control group (NC group), and untransfected TE-13 cells were named as control group. The expression of the BMI-1 mRNA and protein in TE-13 cell s was measured by quantitative real-time PCR and Western blot, respectively. The cell proliferation and the radiosensitivity of TE-13 cells were measured by MTS and colony-forming assay, respectively. Flow cytometry was used to analyze cell cycle and apoptosis. The expression of BCL-2 and BAX in TE-13 cells was measured by Western blot. Comparison between groups was made by analysis of variance. Results: The BMI-1 siRNA group had significantly lower expression of BMI-1 mRNA and protein than the control group and the NC group (P = 0.000, 0.000). The proliferation of TE-13 cells in the BMI-1 siRNA group decreased significantly after irradiation (P = 0.031). The colony-forming assay showed that the BMI-1 siRNA group had a significantly higher radiosensitivity than the control group and the NC group (P = 0.000). After irradiation, the BMI-1 siRNA group had a significantly lower percentage of cells in G₂/M phase than the control group and the NC group (P = 0.000, 0.000). The BMI-1 siRNA group had a significantly increased apoptosis rate (P = 0.000, 0.000), significantly reduced expression of BCL-2(P = 0.000, 0.000), and significantly increased expression of BAX after irradiation (P = 0.000, 0.000). Conclusions: BMI-1 siRNA can inhibit the expression of BMI-1 gene in esophageal cancer TE-13 cells, eliminate the cell cycle arrest in G₂/M phase, induce cell apoptosis after ionizing irradiation in vitro, and increase the radiosensitivity, which may be related to the regulation of the expression of BCL-2 and BAX. (authors)