BMI-1基因对人胰腺癌SW1990细胞放射敏感性影响及机制研究

Effect and possible mechanism of BMI-1 gene on radiosensitivity of human pancreatic cancer SW1990 cell line

目的研究BMI-1对胰腺癌SW1990细胞放射敏感性影响及可能机制。方法选取4 Gy X线及慢病毒下调BMI-1表达作为干预条件,用克隆形成实验观察对SW1990细胞增殖能力的影响,流式细胞仪检测对细胞凋亡及细胞周期的影响,Western blot检测对上皮间充质转化(EMT)的影响。结果克隆形成实验和流式细胞仪发现,与其他组比较,下调BMI-1表达并经4 Gy X线照射后细胞增殖能力最低,凋亡率最高(P<0.05)。流式细胞仪检测细胞周期发现,与对照组相比,4 Gy X线照射后细胞G0/G1期比例下降,G2/M期比例上升(P<0.05);而下调BMI-1后细胞G0/G1期比例上升,G2/M期比例下降(P<0.05)。Western blot发现4 Gy X线照射后E-cadherin表达上调,而Vimentin表达下调(P<0.05)。结论下调BMI-1可增强胰腺癌SW1990细胞放射敏感性,其机制可能与细胞周期及EMT进程相关。

Objective To evaluate the effect and possible mechanism of B-cell-specific moloney murine leukemia virus insertion site 1(BMI-1)on the radiosensitivity of pancreatic cancer SW1990 cell line.Methods According to our previous study results,4Gy X-ray and down-regulation of BMI-1 expression were adopted as intervention conditions.The effect on the proliferation of SW1990 cells was assessed by clony formation assay.The effect on cell apoptosis and cell cycle was evaluated by flow cytometry.The effect upon the epithelial-mesenchymal transition(EMT)was determined by Western blot.Results Clony formation assay and flow cytometry found that the lowest cell proliferation ability and the highest apoptotic rate were obtained after BMI-1 down-regulation and 4Gy X-ray compared with other groups(all P<0.05).Flow cytometry revealed that the proportion of G0/G1 phase was significantly decreased,whereas the G2/M phase was remarkably increased in pancreatic cancer stem cells treated with 4Gy X-ray compared with the control group(both P<0.05).Nevertheless,opposite results were obtained after down-regulation of BMI-1 expression.Western blot showed that the expression of E-cadherin was up-regulated,whereas that of Vimentin was down-regulated following 4Gy X-ray(both P<0.05).Conclusion Downregulation of BMI-1 expression can enhance the radiosensitivity of pancreatic cancer SW1990 cells,and its mechanism may be related to cell cycle and EMT.