不同氧条件下吉非替尼对肺非小细胞肺癌细胞增殖影响.docVIP

不同氧条件下吉非替尼对肺非小细胞肺癌细胞增殖的影响 　　[摘要] 目的 对比研究常氧（21%）、低氧（5%）和高氧（40%）条件下不同浓度吉非替尼（gefitinib）对人非小细胞肺癌（NSCLC）细胞株A549、HCC827、SK-MES-1增殖的影响，并探讨可能的机制。方法 分别在常氧、低氧和高氧条件下以0、10、20、40、60 μmol/L gefitinib处理A549、HCC827、SK-MES-1细胞，培养24 h 后收集细胞， 以CCK-8法检测细胞增殖抑制率；应用实时荧光定量PCR检测HIF-1α mRNA、VEGF-C mRNA、EGFR mRNA的表达情况。 结果 常氧、低氧及高氧条件下，细胞增殖抑制率随吉非替尼浓度的增加、氧浓度的升高而增加（均P0.001）。高氧条件下，与乏氧相关的HIF-1α、VEGF-C、EGFR mRNA在A549细胞、HCC827细胞均明显减弱（P0.05），而SK-MES-1细胞组无统计学意义。结论 吉非替尼可以显著抑制肿瘤细胞增殖，且随着氧浓度增加作用增强，可能机制是提高氧浓度可以进一步下调活化的HIF-1α、VEGF-C、EGFR mRNA的表达。 　　[关键词] 氧浓度；非小细胞肺癌；细胞增殖；吉非替尼；表皮生长因子受体 　　[中图分类号] R59 [文献标识码] A [文章编号] 1674-0742（2015）06（c）-0112-03 　　[Abstract] Objective To investigate the effects of gefitinib on the proliferation of non-small cell lung cancer （NSCLC） cell line A549， HCC827， and SK-MES-1 under different oxygen conditions and explore the underlying molecular mechanism. Methods Under the condition of normal oxygen， low oxygen and high oxygen， Human NSCLC A549， HCC827， SK-MES-1cells were cultured in 0，10，20，40，60μmol/L gefitinib. The cells were collected one day after and cell proliferation inhibition rate were investigated by CCK-8 assay and of real-time fluorescent quantitative PCR was applied to detect the expression of HIF-1α mRNA， VEGF-C mRNA， EGFR mRNA. Results CCK-8 assay results showed that under the condition of normal oxygen， low oxygen and high oxygen， cell proliferation inhibition rate increase with the increasing of the concentration of gefitinib and the rising of oxygen concentration （P0.001） .Under the condition of high oxygen， related to the lack of oxygen of HIF - 1 alpha， VEGF - C， EGFR mRNA in A549 cells， HCC827 cells were significantly reduced （P 0.05）， while SK - MES - 1 cell groups has no statistical significance. Conclusion Gefitinib can significantly inhibit tumor cell proliferation and its effect enhances with the increasing of oxygen concentration. The possible mechanism is that the improvement of the oxygen concentration can further lower the expression of activated H