抑癌基因p16对维A酸诱导肺癌细胞分化作用的影响

Influence of suppressor gene p16 on retinoic acid inducing lung cancer cell A549 differentiation

目的 探讨抑癌基因p16在维A酸 (RA)对肺癌细胞的增殖抑制和分化调控过程中的作用。方法 运用基因转染技术将抑癌基因p16转入人肺癌细胞A5 49中 ,进而以浓度为 5× 10 6mol/L的全反式维A酸 (ATRA)处理转染和未转染p16基因的肺癌A5 49细胞 1～ 4d ,观察A5 49细胞生长 ,流式细胞仪进行细胞周期分析 ,应用免疫组化分析肺组织分化标志物粘蛋白 (MUC1)的变化 ,同时Westernblot观察ATRA对P16蛋白表达的影响。结果 转染p16抑癌基因的A5 49肺癌细胞经ARTA处理后 ,细胞增殖能力明显下降 ,更多的细胞被阻滞于G1/G0 期 ,MUC1的表达下调 ,Westernblot表明经ATRA处理后P16蛋白表达增加。结论 抑癌基因p16能协同RA抑制肺癌A5

Objective To investigate the role of suppressor gene p16 in the process of differential regulation of retinoic acid (RA) on the A549 lung cancer cells.Methods Tumor suppressor gene p16 was transfered into A549 cells and the cells were treated with all trans retinoic acid (ATRA) at the dosage of 5×10 -6 mol/L for 4 d. After that, the proliferation and differentiation of A549 cells were examined by growth curve and cytometry analysis,the change of lung lineage specific marker MUC1 was tested by immunohistochemical staining. Meanwhile, Western blot was used to observe the change of P16 protein expression in A549 cells treated with ATRA.Results ATRA could obviously inhibit the growth and induce the differentiation of A549 cells that were transfered with p16 gene. There were more cells arrested in G 1/G 0 phase and the expression of MUC1 was markedly down regulated than in control cells. The expression of p16 protein was up regulated in A549 cells treated with ATRA Conclusion Suppressor gene p16 could enhance the effects of RA on proliferative suppression and differential induction of A549 cells.