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Anti-tumor Pharmacology

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

Abstract

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 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 maybe closely associated with abrogation of G1 phase arrest.

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Correspondence to Li-cheng Dai.

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Project supported by Zhejiang Province Medicine and Sanitation Research Foundation (No 2003A077).

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Dai, Lc., Wang, X., Yao, X. et al. Antisense oligonucleotide targeting p53 increased apoptosis of MCF-7 cells induced by ionizing radiation. Acta Pharmacol Sin 27, 1453–1458 (2006). https://doi.org/10.1111/j.1745-7254.2006.00405.x

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  • DOI: https://doi.org/10.1111/j.1745-7254.2006.00405.x

Keywords

  • antisense oligodeoxyribonucleotides
  • MCF-7
  • p53 genes
  • radiation tolerance
  • cell cycle

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