Mdm2反义脱氧寡核苷酸抗胶质瘤的机理研究

目的探讨Mdm2反义寡核苷酸(ASODNs)对U251人胶质瘤细胞株的抗肿瘤作用。方法以Lipofectamine介导的Mdm2 ASODNs转染U251细胞,用RT-PCR检测Mdm2 mRNA的改变,流式细胞仪检测细胞周期,Western blot检测野生型p53(wild type p53,wtp53)的表达,研究其抗肿瘤作用。结果Mdm2 ASODNs以不同浓度转染U251细胞后,Mdm2表达减少,细胞增殖抑制程度升高,细胞周期分析显示S期细胞下降,TUNEL法染色观察到明显的凋亡细胞。Western blot检测野生型p53的表达增加。结论Mdm2 ASODNs可提高野生型p53的表达,从而抑制U251细胞增殖,引起细胞周期停滞和诱导凋亡,该作用具有浓度依赖性。

Anti-cancer effect of antisense Mdm2 oligodeoxynucleotide on human glioma cells

Objectives To study the anti-cancer effect of antisense Mdm2 oligodeoxynucleotide on the U251 MG cells. Methods Lipofectamine-mediated antisense Mdm2 ODNs was transfected into U251 MG cells and transfection efficiency was detected by FCM. The expression of Mdm2 mRNA was examined by RT-PCR after ODNs was transfected into cells. MTT assay was used to examine changes in cell proliferation. Apoptosis was evaluated by FCM and TUNEL method, Western blot analysis was used to detect the expression of wild type p53 after ODNs was transfected. Results Mdm2 ODNs were efficiently transfected by Lipofectamine. The expression of Mdm2 mRNA decreased significantly after treatment with antisense ODNs. Antisense ODNs significantly inhibited the proliferation. The cells at S phase decreased in the group treated with antisense ODNs. Apoptosis level and the expression of wild type p53 increased after treated with antisense ODNs. Conclusions Antisense Mdm2 ODNs significantly inhibits the proliferation of U251MG cells and induces their apoptosis in concentration dependent manner.