As_2O_3对人非小细胞肺癌细胞株的增殖抑制及其分子机制

目的观察三氧化二砷(As_2O_3)对非小细胞肺癌腺癌细胞株(A549)的增殖抑制作用及其分子机制。方法体外培养的A549细胞经3μmol/L的As2O3处理5d后,观察细胞形态学、增殖动力学、细胞周期分布及肿瘤相关基因表达改变,并以全反式维甲酸及顺铂作为对照。结果A549细胞经As_2O_3处理后,细胞生长明显减慢,集落形成率显著降低。FCM细胞周期分析:S期细胞显著减少,G0/G1期细胞则明显增加。As_2O_3可使细胞p53、p21表达显著升高而CDKN2明显降低。结论As_2O_3对A549细胞增殖具有显著抑制作用,其分子机制可能是As_2O_3能显著上调p53、p21表达和下调CDKN2的表达而抑制DNA的合成。

Inhibitory effect and underlying molecular mechanism of As2O3 on the growth of human NSCLC cell line

Objective To study the inhibitory effect and underlying molecular mechanism of As2O3 on the growth of human non-small cell lung cancer (NSCLC) cell line. Methods Human lung adenocarcinoma cell line (A549) was treated in vitro with 3 μmol/L As2O3 for 5 d, and compared with control cells treated with all-trans retinoic acid (RA) or DDP for changes in cell morphology, proliferation dynamics, cell cycle distribution and tumor-related gene expression. Results The cell growth and rate of clone formation of A549 cells were markedly inhibited in As2O3 group than in RA group. Flow cytometry demonstrated that S-phase cells decreased and G0/G1 phase cells increased in As2O3 group. Expressions of p53 and p21 were up-regulated obviously but CDKN2 was down-regulated markedly by As2O3. Conclusion As2O3 can inhibit cell growth and clone formation in human NSCLC cell line (A549). The possible molecular mechanism may be inhibition of DNA synthesis through p53/p21 up-regulation and CDKN2 down-regulation.