MUC1胞内段抑制剂GO-201对人肺腺癌A549放射敏感性作用研究

Effect of MUC1 cytoplasmic domain inhibitor on the radiosensitivity of lung cancer cells

摘要:

目的：研究MUC1胞内段（MUC1-CT）抑制剂GO-201对人肺腺癌A549细胞放射敏感性影响。方法：MTT检测不同剂量以及不同时间GO-201对肺腺癌A549细胞的增殖抑制率；克隆形成实验检测GO-201对A549细胞放射增敏作用，单击多靶模型拟合细胞存活曲线并计算Dq、D0、SF2值和放疗增敏比（sensitizing enhancing vatio，SER）；流式细胞术检测各实验组细胞活性氧水平，Western blot法检测锰超氧化物歧化酶（manganese superoxide dismutase，MnSOD）表达变化。结果：MUC1-CT抑制剂GO-201可抑制肺腺癌A549细胞的增殖，其作用24、48、72 h IC50值分别是30.79、23.32、13.60 ?滋mol/L。并且对肺腺癌A549细胞具有放射增敏作用，其放疗增敏比SER为1.14；联合照射组中，A549细胞活性氧水平明显升高（F=12.019，P=0.008），Mn－SOD蛋白表达量明显下降（F=5.465，P=0.048），与对照组比较差异具有统计学意义。结论：MUC1-CT抑制剂GO-201可增加人肺腺癌A549细胞的放射敏感性。

Abstract:

Objective：To explore the radiosensitive effect of GO-201 on lung cancer cell line A549 cultured in vitro. Methods：MTT assay was used to detect the growth inhibition rate；the radiosensitive effect was detected by clone formation test. Cell survival cure was fitted by multitarget one-hit model and Dq，D0，SF2，sensitizing enhancing ratio（SER） was calculated. Additionally，flowcytometry and Western blot were also conducted to observe the influence of GO-201 and radiation on cell reactive oxygen species and the expression of manganese superoxide dismutase（MnSOD） protein. Results：GO-201 could inhibit the proliferation of lung cancer cell（IC50 value were 30.79 ?滋mol/L，23.32 ?滋mol/L，13.60 ?滋mol/L after 24，48，72 h） and enhance radiosensitivity of A549 cells；the SER was 1.14. Reactive oxygen level of A549 cell was increased（F=12.019，P=0.008） and the expression of MnSOD protein was decreased（F=5.465，P=0.048） in combination group than in control group. Conclusion：Inhibiting MUC1 cytoplasmic domain can improve the radiosensi-tivity of lung cancer cell.