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iASPP对表达野生型p53基因的乳腺癌细胞株MCF-7凋亡的影响 被引量:5

iASPP on apoptosis in breast cancer cells which expressed wild type p53
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摘要 目的:P53凋亡刺激蛋白(ASPP)家族成员能够调节P53诱导的细胞凋亡。其中ASPP家族抑制成员(iASPP)主要通过特异性地和P53蛋白结合抑制肿瘤细胞的凋亡,本实验通过构建iASPP的RNAi质粒,研究在体内外抑制iASPP基因后对表达野生型p53基因的乳腺癌细胞MCF-7凋亡的影响。方法:采用分子生物学方法构建iASPP的腺病毒RNAi质粒pAd-iASPP-RNAi;体外转染MCF-7细胞,同时建立MCF-7细胞的裸鼠移植瘤模型;分别采用RT-PCR和Western blotting检测转染后瘤细胞iASPP mRNA和蛋白质表达的变化;采用流式细胞术检测转染前后瘤细胞凋亡的变化。结果:转染iASPPRNAi后,MCF-7细胞的iASPP mRNA及蛋白表达量降低(抑制率分别为95.4%和96.8%,P<0.01);MCF-7细胞的凋亡百分率、坏死百分率与对照组相比具有显著差异(P<0.01)。裸鼠移植瘤模型经pAd-iASPP-RNAi处理后,iASPP mRNA及蛋白表达量也明显降低(抑制率分别为87.4%和89.2%,P<0.01);移植瘤细胞的凋亡百分率和坏死百分率显著上升(P<0.01和P<0.05)。结论:在体内外抑制iASPP基因的表达能够通过p53途径诱导表达野生型p53的乳腺癌细胞凋亡。 AIM: To investigate the RNAi effect of the inhibitory member of the ASPP family (iASPP) on the apoptosis of human breast cancer cell MCF - 7 which expressed the wild type p53 gene. METHODS : The recombinant plasmid pad - iASPP - RNAi was transfected into MCF - 7 cells. The expression of iASPP mRNA and protein was analyzed by RT-PCR and Western blotting, respectively. The cell apoptosis was detected by FCM, and then the MCF-7 cells were transplanted into nude mice to set up transplantation model. The expression of iASPP RNA and protein in transplanted neoplasm were determined by RT - PCR and Western blotting, the apoptosis index was detected by FCM at the same time. RESULTS: The results showed that the expression of iASPP descended in MCF -7 cells (mRNA 95.4% and protein 96. 8%, respectively, P 〈 0.01 ) and the apoptosis rate and necrosis rate of MCF - 7 cells increased ( P 〈 0. 01 ) after transfection. As treated with pAd - iASPP - RNAi, the expression of iASPP in transplantation tumor cells descended 87.4% (mRNA) and 89. 2% (protein), respectively (P 〈0. 01 ), and the apoptosis rate and necrosis rate increased accordingly (P 〈 0. 01, P 〈 0. 05). CONCLUSION: The inhibition of iASPP may resume the ability of p53 to induce apoptosis in breast cancer cells which is able to express wild type p53.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2010年第2期282-286,共5页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资助项目(No.30672299)
关键词 蛋白质iASPP MCF-7细胞 基因 P53 RNA干扰 Protein iASPP MCF - 7 cells Genes ,p53 RNA interference
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