AZD8055对耐照射胰腺癌细胞逆转作用的研究

Study of reversion effect of AZD8055 on the resistance irradiation of pancreatic cancer

目的：将 AZD8055作用于耐照射胰腺癌细胞，研究其对耐照射胰腺癌细胞的逆转作用。方法通过梯度照射方法培养耐照射 Panc-1胰腺癌细胞株，检测其亲本细胞株及耐照射细胞株的哺乳动物雷帕霉素靶蛋白（mTOR 蛋白）和 S6K1蛋白的表达情况。经过 AZD8055作用，再次行 X 线照射检测其被杀伤情况。结果成功建立耐照射胰腺癌细胞株，其 mTOR 蛋白和 S6K1蛋白表达均较亲本细胞株增强，经过 AZD8055处理的细胞株，其mTOR 蛋白和 S6K1蛋白表达降低，表现出对 X 线照射敏感性恢复。细胞凋亡增加，其细胞凋亡率与 mTOR 蛋白和S6K1蛋白表达呈现负相关，与 AZD8055作用时间呈正相关，而 mTOR 蛋白和 S6K1蛋白表达呈正相关。结论 AZD8055处理可逆转耐照射胰腺癌细胞的耐照射性，与 AZD8055抑制 mTOR 蛋白表达相关联，考虑作为mTOR 下游基因，S6K1与其协同参与胰腺癌照射抵抗的发生。

Objective To study the reverse effect of AZD8055 on the radioactivity resistance of pancreatic cancer cell. Methods The radioactivity resistance of pancreatic cancer cell Panc-1 was developed through the gradient irradiation. The protein expression of mTOR and S6K1 were tested both in parental cell and radioactivity resistance cell. Radioactivity resistance cell was processed by X-ray again after managed by AZD8055 and the killing was tested. Results Radiation resistance of pancreatic cancer cell lines was successfully established. The protein expression strength of mTOR and S6K1 of experiment group was higher than parental cell. The protein expression strength of mTOR and S6K1 tended to weaken after processed by AZD8055. Radiation resistance to X-ray turned recovery. Cell of apoptosis increased. The cell apoptosis rate was negatively correlated with the protein expression strength of mTOR and S6K1. The cell apoptosis rate was positively correlated with the time of procession of AZD8055. The cell apoptosis rate was negatively correlated with the protein expression strength of mTOR and S6K1. Conclusions The feature of radiation resistance is reversal after processed by AZD8055, which is correlated with the suppression of the expression of mTOR protein. S6K1 maybe the downstream genes of mTOR participating the occurring of the resistance irradiation of pancreatic cancer cell.