Mechanism of p38MAPK Signal Pathway on Chemosensitivity of Glioma Drugresistance Cells
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摘要: 探讨p38MAPK信号通路在脑胶质瘤细胞化疗耐药中的作用及相关机制。 方法 在前期建立U251/TMZ胶质瘤耐药细胞株的基础上，用特异性阻断剂SB203580阻断耐药细胞株中p38MAPK信号通路，替莫唑胺作用下检测耐药株的细胞活性变化，同时检测MDR1、TopoⅡ、BCL-2 等耐药相关基因的蛋白表达变化。 结果 阻断通路后替莫唑胺作用下细胞的抑制率明显低于未阻断组，两组之间比较差异有统计学意义（P＜0.05），阻断后耐药细胞中BCL-2、MDR1的表达明显升高，TopoⅡ的表达明显降低，与未阻断的耐药细胞相比较差异有统计学意义（P＜0.05）。结论 U251/TMZ胶质瘤耐药细胞中p38MAPK信号通路被阻断后细胞的耐药性增强，其机制可能与耐药株中耐药相关基因BCL-2、TopoⅡ、MDR1的表达变化有关。
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关键词:
- 化疗耐药 /
- p38MAPK信号通路 /
- 胶质瘤
Abstract: Objective To investigate the mechanism of p38MAPK signal pathway on chemosensitivity of glioma drug-resistance cells. Methods After the U251/TMZ resistant glioma cell line was established,p38MAPK signaling pathway was blocked with the specific inhibitor SB203580. Cell activity was detected by MTT. Expression changes of MDR1, BCL-2 and TopoⅡ were detected by Western blot. Results The activity of drug-resistance cells was improved significantly after the signal pathway was blocked. With different concentrations of TMZ, the expression of BCL-2 and MDR1 were increased while TopoⅡ expression was decreased significantly in blocked group,compared with unblocked group, with significant difference (P＜0.05). Conclusion Blocked p38MAPK signaling pathway activates the chemosensitivity of glioma drug-resistance cells, and the mechanism may be related to the changes of MDR1, BCL -2 and TopoⅡ expression.-
Key words:
- Drug-resistance /
- p38MAPK signal pathway /
- Glioma
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