COX-2抑制剂塞来昔布提高人结肠癌细胞SW480的放射敏感性

COX-2 inhibitor celecoxib improves radiosensitivity of human colon carcinoma cell line SW480

目的:探讨COX-2抑制剂塞来昔布对人结肠癌细胞SW480放射增敏的作用机制.方法:体外培养结肠癌细胞SW480.COX-2抑制剂塞来昔布作用SW480细胞24h,X线不同剂量照射,克隆形成法计算细胞存活率,单击多靶模型拟合细胞存活曲线,计算Dq、D0、SF2值和放射增敏比(SER);X线6Gy照射后,流式细胞仪检测细胞凋亡变化,应用Western blot方法检测磷酸化Akt、COX-2、磷酸化Bad蛋白的表达.结果:celecoxib联合照射组的Dq、D0及SF2均明显低于单纯照射组(0.995vs2.527,1.091vs1.622,0.352vs0.805,均P<0.05),celecoxib联合照射组SER为1.487;照射能够提高pAkt、COX-2和pBad的表达,celecoxib联合照射组pAkt、COX-2和pBad表达低于单纯照射组;celecoxib联合照射组SW480的细胞凋亡率明显高于单纯照射组(15.02±2.16vs6.25±1.22,P<0.05).结论:celecoxib能够抑制PI3K/Akt/COX-2途径的活化,从而提高SW480细胞放射治疗的效果.

AIM：To determine whether celecoxib,a selective cyclooxygenase-2 （COX-2） inhibitor,can improve radiosensitivity of human colon carcinoma cell line SW480.METHODS：Cultured SW480 cells were treated with celecoxib for 24 h and then irradiated with different doses of X-rays.Cell survival was evaluated by colony formation assay.To calculate Dq,D0,SF2 and SER,the cell survival curve was fitted by the one-hit multi-target model.After 6-Gy radiation,the apoptosis of SW480 cells wasdetected by flow cytometry,and the expression of pAkt,COX-2,and pBad in SW480 cells was detected by Western blot.RESULTS：The Dq,D0 and SF2 values for irradiated SW480 cells pretreated with celecoxib were lower than those for unpretreated ones （0.995 vs 2.527,1.091 vs 1.622 and 0.352 vs 0.805,respectively;all P〈 0.05）.The SER for irradiated SW480 cells pretreated with celecoxib was 1.487.X-ray radiation enhanced the expression of pAkt,COX-2 and pBad proteins in SW480 cells.The expression levels of pAkt,COX-2 and pBad proteins in irradiated SW480 cells pretreated with celecoxib were lower than those in unpretreated ones.The apoptosis rate was significantly higher in irradiated SW480 cells pretreated with celecoxib than in unpretreated ones （15.02 ± 2.16 vs 6.25 ± 1.22,P〈 0.05）.CONCLUSION：Celecoxib improves radiosensitivity of human colon carcinoma cell line SW480 perhaps by inhibiting the activation of the PI3K/Akt/COX-2 pathway.