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目的研究替莫唑胺(TMZ)抑制大鼠C6胶质瘤增殖及对p53、caspase3蛋白表达的影响。方法 120只SD雄性大鼠,构建C6胶质瘤模型。荷瘤大鼠随机平均分为模型组、生理盐水组、替莫唑胺组。处理15 d后检测脑胶质瘤的体积和重量;ELISA检测白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及血管内皮生长因子(VEGF)表达水平;分离脑胶质瘤细胞,用流式细胞仪检测各组细胞凋亡情况;Western-blot检测脑胶质瘤中p53、Cleaved-caspase-3、Bax蛋白表达情况。结果生理盐水组与模型组各项检测均无明显差异(P>0.05)。与模型组相比,替莫唑胺处理后脑胶质瘤体积明显减少(P<0.01),脑胶质瘤的重量也明显降低(P<0.05),IL-6、TNF-α、VEGF表达显著降低(P<0.05),胶质瘤细胞的凋亡率明显升高(P<0.01),p53、Cleaved-caspase-3、Bax蛋白表达明显上升(P<0.01)。结论替莫唑胺可能通过活化凋亡信号途径p53/Bax/caspase-9/caspase-3促进胶质瘤细胞凋亡,抑制大鼠C6胶质瘤细胞增殖。
Objective To study the effect of temozolomide (TMZ) on the proliferation and the expression of p53 and caspase 3 in rat C6 glioma. Methods 120 SD male rats were established C6 glioma model. Tumor-bearing rats were randomly divided into model group, normal saline group and temozolomide group. The volume and weight of glioma were detected 15 days after treatment. The expression of IL-6, TNF-α and VEGF were detected by ELISA. The apoptosis of glioma cells was detected by flow cytometry. The protein expressions of p53, Cleaved-caspase-3 and Bax in gliomas were detected by Western-blot. Results There was no significant difference between the saline group and the model group (P> 0.05). Compared with the model group, the volume of brain glioma was significantly decreased (P <0.01), the weight of glioma was significantly decreased (P <0.05), the expression of IL-6, TNF- <0.05). The apoptosis rate of glioma cells was significantly increased (P <0.01), and the protein expressions of p53, Cleaved-caspase-3 and Bax were significantly increased (P <0.01). Conclusion Temozolomide can promote the apoptosis of glioma cells and inhibit the proliferation of C6 glioma cells through the activation of apoptotic signaling pathway p53 / Bax / caspase-9 / caspase-3.