9-顺-维A酸对肺鳞癌细胞株A2细胞周期、凋亡及相关基因表达的影响  

Effect of 9-cis-retinoic acid on cell cycle, apoptosis and related gene expression in human lung squamous carcinoma cell line A2

作　　者：游庆军[1] 沈振亚[2] 于雪艳[3] 胡国强[3] 金小寅[1] 蒋锡初[1] 

机构地区：[1]苏州大学附属第四医院胸心外科,江苏无锡214062 [2]苏州大学附属第一医院胸心外科 [3]山东大学医学院

出　　处：《中华实验外科杂志》2003年第12期1121-1122,共2页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(39770730)

摘　　要：目的 探讨9-顺-维 A酸(9-cis RA)对肺鳞癌细胞株A2细胞周期影响和诱导凋亡作用并检测细胞周期相关基因 Cyclin D1、Rb的表达,探讨9-cis RA的抗癌作用机制。方法 体外培养 A2细胞,随机分为两组,实验组加入 9-cis RA使其终浓度为 5μmol/L,对照组加入二甲亚砜使其终浓度为 0.1％,两个组别均按 0、12、24、36、48、72 h共 6个时相培养,用流式细胞仪技术分别检测肿瘤细胞G0/G1期比率、S期比率及凋亡发生率,同时检测Cyclin D1、Rb基因表达率,作对比研究。结果 9-cis RA作用于肺癌细胞 A2后 G0/G1期细胞比率增高,S期细胞比率下降。9-cis RA作用于 A2细胞后凋亡发生率明显升高,Rb基因表达增强,Cyclin D1基因表达受抑制,在 48 h时药物作用达最高峰。凋亡发生率与Rb基因表达呈正相关(r=0.647,p<0.05),与Cyclin D1基因表达呈负相关(r=-0.723,P<0.05)。结论 9-cis RA可能通过激活 Rb基因表达和抑制 Cyclin D1基因表达途径使肺癌细胞明显阻滞在 G0/G1期,抑制肺癌细胞增殖。9-cis RA可明显诱导肺癌细胞调亡,Rb和Cycin D1基因同样在其中发挥着重要作用。Objective To study the effect of 9-cis-retinoic acid on cell cycle, apoptosis and Cyclin D1, Rb gene expression in lung squamous carcinoma cell line A2. Methods In Vitro, A2 was divided into two groups randomly: group A was treated with 5 μmol/L 9-cis RA; group B was treated with 0. 1 % dimethylsulfoxid. After incubation for 0, 12, 24, 36, 48, 72 h, the cell cycle, apoptosis and the expression of Cyclin D1 and Rb genes were detected by FACS technique. Results 9-cis RA increased the ratio of cells in G0/G1 status and decreased the ratio of cells in S status. 9-cis RA induced apoptosis significantly, enhanced Rb gene expression and inhibited Cyclin D1 gene expression. Apoptosis had positive relationship with Rb gene expression (P < 0. 05), and had negative relationship with Cyclin D1 gene expression (P < 0. 05). Conclusion 9-cis RA can arrest A2 cells in G0/G1 status by Rb up-regulation and Cyclin D1 down-regulation, then inhibit A2 cell growth. 9-cis RA induces A2 cells apoptosis, and Cyclin D1 and Rb gene play an important role in this progress.

关 键 词：9-顺-维A酸 肺鳞癌 A2细胞 细胞凋亡 基因表达 癌细胞株 细胞周期 

分 类 号：R734.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]