西妥昔单抗对三阴性乳腺癌细胞的放射增敏作用的机制研究

Study of the mechanism of radiation sensitizing effect of cetuximab on breast cancer cell

目的对以往研究发现的西妥昔单抗(C225)对乳腺癌细胞的放射增敏作用的机制进行探讨。方法取指数生长期的三阴性乳腺癌MDA-MB-231细胞,分正常对照组、单独药物组(30nmol/L C225)、单独照射组(8Gy X线)和联合处理组(30nmol/L C225+8Gy X线)。通过蛋白印迹法检测C225与X线联合应用对p-表皮生产因子受体(EGFR)蛋白以及下游信号蛋白p-Akt、p-P38表达的影响以及对凋亡相关基因胱天蛋白酶(caspase)-3蛋白表达。结果蛋白印迹法结果显示C225与X线联合应用时,可使细胞p-EGFR信号蛋白表达下降,对pAkt和p-P38蛋白表达有明显抑制作用,同时使caspase-3蛋白表达显著增强。结论 C225对人乳腺癌MDA-MB-231细胞的放射增敏作用可能是与EGFR下游信号蛋白Akt、MAPK磷酸化活性降低,以阻断PI3K/Akt信号通路的活化,以及增加肿瘤细胞对放射线的凋亡反应有关。

Objective To discuss the mechanism of radio‐sensitization of cetuximab（C225） on breast cancer cells .Methods MDA‐MB‐231 cells in logarithmic phase were divided into four groups ：control group ,drug group （30 nmol/L C225） ,radiation group （8 Gy X ray） and C225 plus radiation .Western blotting was used to detect the expression of p‐EGFR ,p‐Akt ,p‐P38 and caspase‐3 ,respectively .Results The combination of C225 and radi‐ation could decrease the expression of p‐EGFR and its downstream singling pathway proteins such as p‐Akt ,p‐P38 .Western blotting also showed that the expression of caspase‐3 was strengthened in C225 plus radiation group .Conclusion The mechanism of radio‐sensitization of MDA‐MB‐231 cells may be attributed to the inhibition of EGFR signaling pathway ,the down‐regulation of the PI3K/Akt signaling pathway and the enhancement of radi‐ation‐induced apoptosis .