靶向MDM2反义寡核苷酸对乳腺癌MCF-7细胞株紫杉醇药物敏感性的影响

Effects of the MDM2 antisense oligonucleotide on chemosensitivity to paclitaxel in human breast cancer cells MCF-7

目的探讨靶向MDM2基因的反义寡核苷酸(ASON)对MCF-7细胞株乳腺癌紫杉醇药物敏感性的影响。方法人工合成一段针对MDM2 mRNA的反义寡核苷酸及错义寡核苷酸,采用脂质体介导MDM2 ASON转染MCF-7乳腺癌细胞系,RT-PCR和Western blot方法检测其抑制效率,MTT观察细胞给药后的增殖能力。结果 MDM2 ASON转染细胞,给予紫杉醇处理后,MDM2 mRNA和蛋白表达下调,其中A500下调最显著,细胞增殖抑制率明显增高,其中A500抑制率高达(13.0±0.84)%。结论 ASON转染细胞后,下调MDM2的表达,促进凋亡,提高了对紫杉醇的敏感性,为乳腺癌治疗提供了新疗法。

Objective To investigate the effects of the MDM2 antisense oligonucleotide （ASON） on chemosensitivity to paclitaxel in human breast cancer cells MCF-7. Methods ASON and missense oligonucleotides were synthesized, MCF-7 cell lines was transfected by li- posome-mediated ASON, the inhibition efficiency was detected by RT-PCR and Western blot, proliferation of cells was observed by MTT. Results ASON transfected MDM2 mRNA and pro- tein expressions were significantly reduced after paclitaxel treatment, A500 was the most signif- icant, proliferation inhibition rate was significantly higher, and A500 inhibition rate was （ 13.0 ±0. 84）%. Conclusion ASON effectively suppresses the expression of MDM2 mRNA, in- creases apoptosis and enhances the chemosensitivity to paclitaxel in MCF-7, which provides a new treatment for breast cancer therapy.