,Antisense oligonucleotide targeting p53 increased apoptosis of MCF-7 cells induced by ionizing radi

• 作 者: Li-cheng DAI Xiang WANG Xing YAO Li-shan MIN Fu-chu QIAN Jian-fang HE
• 机 构: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, China
• 出 处: 中国药理学报（英文版）
• 发表日期: 2006年11期
• 关键词: antisense oligodeoxyribonucleotides MCF-7 p53 genes radiation tolerance cell cyc

Aim: To investigate the effect of antisense compounds (AS) targeting human p53 mRNA on radiosensitivity of MCF-7 cells. Methods: Weste blotting and RT-PCR were used to analyze the protein content and mRNA level. Additionally, cell proliferation, cell cycle and cell apoptosis were all analyzed in irradiated or sham-irradiated cells. Results: Among the five antisense compounds (AS), AS3 was identified to efficiently inhibit p53 mRNA level and protein content. Interestingly, ASS transfer has little effect on cell proliferation in DU-145 cells (mutant p53) after ionizing radiation (IR). In contrast, a marked increase of cell apoptosis and growth inhibition were observed in MCF-7 cells (wild-type p53), suggesting that AS3 can increase radiosensitivity of MCF-7 cells. Additionally, it was also observed that the transfection of AS3 decreased the fraction of G1 phase cells, and increased the proportion of S phase cells compared to untreated cells 24 h after IR in MCF-7 cell lines. Conclusion: AS3 transfection increases MCF-7 cell apoptosis induced by 5 Gy-radiation, and this mechanism may be closely associated with abrogation of G1 phase arrest.