Mcl-1反义寡核苷酸调控Hela细胞生物学功能及对化疗敏感性的影响

Effect of Mcl-1 antisense oligonucleotide on Hela cell biology and sensitivity of chemotherapy

目的:探讨髓样细胞白血病-1(myeloid leukemia-1,Mcl-1)基因对宫颈癌Hela细胞增殖与凋亡的调控作用及其对宫颈癌化疗敏感性的影响。方法:通过脂质体瞬时转染Mcl-1反义寡核苷酸(antisense oligo-nucleotide,AS-ODN)至Hela细胞;用Western印迹检测Mcl-1表达水平;采用MTT法和流式细胞分析技术分别检测Hela细胞的增殖和凋亡情况。结果:Mcl-1 AS-ODN可明显抑制Hela细胞增殖,阻滞细胞G1/S期进程,并且促进细胞凋亡。Hela细胞对化疗敏感性普遍偏低,然而在Mcl-1 AS-ODN抑制Mcl-1表达后,化疗药物诱导细胞凋亡率和生长抑制率显著增加。结论:Mcl-1 AS-ODN能够抑制Hela细胞增殖并促进其凋亡,而且能够增加Hela细胞对化疗药物敏感性。提示Mcl-1有可能成为辅助宫颈癌化疗新的分子靶点。

Objective To explore the effect of myeloid leukemia-1（Mcl-1） gene on the proliferation and apoptosis of Hela cells and the sensitivity of cervical cancer chemotherapy by antisense technology.Methods Mcl-1 antisense oligonucleotide（AS-ODN）was transfected into Hela cells with lipofectamine 2000.The expression of Mcl-1 was analyzed by Western blot,the cell viability was detected by MTT assay,and apoptosis was evaluated by flow cytometry.Results Mcl-1 AS-ODN arrested the cell cycle at G1/S,greatly inhibited the cell growth and induced apoptosis.The sensitivity of Hela cells on chemotherapy was low.There was obvious increase in the apoptosis rate by chemotherapy drugs and growth inhibition rate after inhibiting the expression of Mc1-1.Conclusion Mcl-1 AS-ODN can not only inhibit Hela cell proliferation and induce apoptosis,but also increase the sensitivity of chemotherapy.Mcl-1 may be a potential target gene for cervical cancer chemotherapy.