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目的探讨MDM2反义寡核苷酸联合紫杉醇对U251人胶质瘤细胞株的作用。方法以Lipofectamine介导的MDM2反义寡核苷酸转染U251人胶质瘤细胞株,免疫组织化学法检测胶质瘤细胞株MDM2蛋白的改变,噻唑蓝(MTT)检测细胞增殖,流式细胞仪检测凋亡,Western blot检测野型生p53(wild type p53,wtp53)的表达,构建荷胶质瘤裸鼠模型,采用瘤内注射和腹腔给药方式,以MDM2反义寡核苷酸联合紫杉醇治疗,研究其联合抗肿瘤作用。结果脂质体介导反义MDM2 ODN转染U251人胶质瘤细胞株后,MDM2表达减少,与紫杉醇联合使用可增加细胞的凋亡率,野型生p53的表达量增加,裸鼠动物试验联合治疗组瘤重显著小于单独用药组及对照组。结论MDM2反义寡核苷酸可显著降低MDM2在U251中的表达,引起细胞凋亡,MDM2反义寡核苷酸与紫杉醇联合作用U251人胶质瘤细胞株具有协同作用。
Objective To investigate the effect of MDM2 antisense oligonucleotide and paclitaxel on U251 human glioma cell line. Methods U251 human glioma cell line was transfected with Lipofectamine-mediated MDM2 antisense oligonucleotide. The changes of MDM2 protein in glioma cell line were detected by immunohistochemistry. Cell proliferation was detected by MTT assay. Flow cytometry The expression of wild type p53 (wtp53) was detected by Western blot, and the model of glioma-bearing nude mice was constructed. The tumor cells were treated with intratumoral injection and intraperitoneal injection of MDM2 antisense oligonucleotide Paclitaxel treatment, study its combined anti-tumor effect. Results The liposome-mediated antisense MDM2 ODN transfected U251 human glioma cell line, MDM2 expression decreased with the combination of paclitaxel can increase the rate of apoptosis, wild-type p53 increased expression of the nude mice in animal experiments The tumor weight of the combined treatment group was significantly less than that of the single treatment group and the control group. Conclusion MDM2 antisense oligodeoxynucleotides can significantly reduce the expression of MDM2 in U251 and induce apoptosis. MDM2 antisense oligodeoxynucleotide has a synergistic effect with paclitaxel in U251 human glioma cell line.