三氧化二砷诱导小细胞肺癌细胞凋亡及p53、bcl-2基因表达的研究

目的：研究三氧化二砷（As2O3）诱导小细胞肺癌细胞凋亡及其机制。方法：采用末端脱氧核苷酰转移（TUNEL）法检测细胞凋亡，免疫组织化学（SABC）法分析As2O3对小细胞肺癌细胞（NeI-H细胞）p53、bcl-2基因蛋白表达的影响。结果：As2O30.5μmol/L、1.0μmol/L、2.0μmol/L作用72h，NeI-H细胞均可呈现凋亡所特有的亚G1峰，凋亡比率随药物作用浓度增加和作用时间延长而增高。实验组p53基因蛋白表达较对照组明显增多，药物浓度越高表达越多（P=0.001）；bcl-2基因蛋白表达较对照组明显减少，药物作用浓度越高表达越少（P=0.001）。结论：As2O3抗肿瘤作用主要是通过诱导细胞凋亡实现的，其机制与上调p53基因表达及下调bcl-2基因表达有密切关系。

Arsenic trioxide induced apoptosis and expression of p53 and bcl-2 genes in human small cell lung cancer cells

OBJECTIVE: To study the arsenic trioxide (As(2)O(3)) induced apoptosis in a human small cell lung cancer cell line (NeI-H cells) and its possible mechanisms. METHODS: Apoptotic cells were detected by the TUNEL method. The expression of p53 and bcl-2 was analyzed with immunohistochemical staining. RESULTS: NeI-H cells showed the sub-G(1) peak after treatment with As(2)O(3) (0.5 micromol/L, 1.0 micromol/L, and 2.0 micromol/L) for 72 hours. The ratio of apoptotic cells increased with the increasing concentrations of the drug and the time of culture. Immunohistochemical staining of NeI-H cells showed increased expression of p53, but decreased expression of bcl-2 with the increasing concentrations of the drug. CONCLUSION: The anti-carcinogenic effect of As(2)O(3) is due to the induction of cell apoptosis. Up-regulation of the p53 gene and down-regulation of the bcl-2 gene may be an underlining mechanism.