摘要
目的:探讨p38 MAPK抑制剂通过Akt(蛋白激酶B)有关的信号途径对结肠癌细胞阿霉素(Doxorubicin)化疗敏感性的影响.方法:应用阿霉素(Dox)和p38 MAPK特异性抑制剂SB203580及两者联合应用去处理结肠癌HCT-116细胞株.采用MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]法检测化疗药物对肿瘤细胞的生存抑制率,Western blot蛋白免疫印迹技术检测化疗药物处理后癌细胞Akt和磷酸化Akt的表达水平.结果:MTT显示阿霉素和抑制剂SB203580对结肠癌细胞均有抑制作用(26.60%,33.87%),后者大于前者,两者相同用量联合后癌细胞抑制率更明显(56.04%).Western blot显带说明阿霉素处理组较联合组的Akt表达水平并无明显差异,而磷酸化的Akt水平较SB203580组和联合组显著升高.亦即抑制剂组和联合组方案可降低结肠癌细胞磷酸化Akt的表达水平.结论:p38 MAPK抑制剂SB203580可能通过阻断P13K/Akt信号途径或其他有关Akt的通路以提高结肠癌细胞阿霉素化疗的敏感性.
AIM:To evaluate whether SB203580,a p38MAPK inhibitor,reduces resistance of colon cancer HCT116 cells to doxorubicin and to explore possible mechanisms involved.METHODS:Doxorubicin alone or in combination with SB203580 was used to treat subcultured HCT-116 cells.After treatment,cell growth was determined by MTT assay,and Akt and p-AKt expression was detected by Western blotting.RESULTS:Either doxorubicin or SB203580 inhibited HCT-116 cell growth,and the latter had a stronger inhibitory effect than the former (26.60% vs 33.87%).Combined use of doxorubicin and SB203580 had more strong inhibitory effect than treatment with either of them alone (56.04%).Expression of Akt showed no significant difference between cells treated with doxorubicin alone and those treated with combined doxorubicin and SB203580,while the phosphorylation of Akt was significantly higher in the doxorubicin group than in the combination group.CONCLUSION:The p38 MAPK inhibitor SB203580 could block the Akt signaling pathways and increase the sensitivity of colon cancer cells to doxorubicin.
出处
《世界华人消化杂志》
CAS
北大核心
2012年第2期145-148,共4页
World Chinese Journal of Digestology