三氧化二砷对肺腺癌化学治疗敏感性的影响及其机制

目的　研究三氧化二砷 (As2 O3)对肺腺癌细胞生长过程及化学治疗 (简称化疗 )敏感性的影响。方法　应用四甲基偶氮唑蓝 (MTT)比色、免疫组织化学、流式细胞仪、逆转录 聚合酶链反应(RT PCR)等方法 ,观察不同浓度As2 O3 对人肺腺癌A549细胞株生长、化疗敏感性、细胞周期 ,及凋亡基因Fas/FasL、抗凋亡基因B淋巴细胞白血病 2 (bcl 2 )和多药耐药相关蛋白 (MRP)、肺耐药蛋白 (LRP)表达水平的影响。结果　 1、2 μmol/L的As2 O3 对人肺腺癌A549细胞株的生长抑制作用较弱 ,但能显著提高A549细胞对顺铂的敏感性 (P <0 .0 5)、提高A549在G1期细胞的比率 ,上调Fas、下调bcl 2及MRP、LRP的表达水平。 5μmol/L的As2 O3 对人肺腺癌A549细胞有一定的抑制作用 ,并可上调bcl 2、MRP、LRP的表达水平 ,但不能提高A549细胞对顺铂的敏感性。结论　低浓度的As2 O3 可能通过提高A549细胞在G1期的比率 ,上调Fas基因和下调bcl 2、MRP、LRP基因的表达水平 ,提高肺腺瘤细胞对化疗的敏感性

Effect and mechanism of arsenic trioxide on chemosensitivity of human lung adenocarcinoma cells

OBJECTIVE: To study the apoptosis and chemosensitive effect of As(2)O(3) on human lung adenocarcinoma cell line A549. METHODS: MTT colorimetric assay, immunohistochemical method, flow cytometry and RT-PCR were applied to observe the different effects induced by As(2)O(3) with different concentrations on A549 cells. RESULTS: 1, 2 micro mol/L As(2)O(3) increased Fas expression and inhibited the expression of bcl-2, MRP and LRP; G(1) arrest was observed and the cells were more sensitive to cisplatin. A549 cells in the presence of 5 micro mol/L As(2)O(3) showed growth inhibition and up-regulation of bcl-2, MRP and LRP expressions; but their chemosensitivity to cisplatin did not change. CONCLUSION: As(2)O(3) in low concentrations can increase the chemosensitivity of A549 cells by regulating the expression of apoptosis genes, anti-apoptosis genes and drug-resistant genes and affecting the cell cycle progress.