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

Autor: Xiang Wang, Li-cheng Dai, Xing Yao, Fu-chu Qian, Li-shan Min, Jian-fang He
Rok vydání: 2006
Předmět:
Zdroj: Acta pharmacologica Sinica. 27(11)
ISSN: 1671-4083
Popis: Aim: To investigate the effect of antisense compounds (AS) targeting human p53 mRNA on radiosensitivity of MCF-7 cells. Methods: Western 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, AS3 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 G 1 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 maybe closely associated with abrogation of G 1 phase arrest.
Databáze: OpenAIRE