低氧时肺癌细胞侵润和迁移特性的变化及分子基础

Effect of hypoxia on invasion and migration of lung carcinoma cells and its molecular basis

目的 :探讨低氧对肺癌细胞侵润、迁移特性的影响及其机制。方法 :将肺癌细胞株置常氧 (空气、5 %CO2 )、低氧 (5 %O2 、5 %CO2 、90 %N2 )、无氧 (95 %N2 、5 %CO2 )的不同氧环境中培养 4 8h后 ,用划痕法测定各组细胞的迁移能力 ,用羊膜内皮细胞模型测定各组细胞的侵润能力。同时将处理的细胞接种于裸鼠背部皮下 ,观察其生长情况及转移特点。同时分析上皮钙粘附素、β1-整合素的表达量。 结果 :低氧组细胞迁移能力、侵润能力显著高于常氧组。无氧组成瘤率和肺转移率显著低于常氧组和低氧组。低氧组上皮钙粘附素表达显著低于常氧组而 β1-整合素表达量显著高于常氧组 ,无氧组两者均显著低于常氧组。结论 :适度低氧可以下调肺癌细胞上皮钙粘附素表达 ,增加 β1-整合素表达 ,增强癌细胞迁移力和侵润力。但是严重低氧使癌细胞粘附分子表达下降 ,生长增殖能力、迁移力和侵润力下降。

AIM: To investigate the effect of hypoxia on the invasion and migration of lung carcinoma cells. METHODS: Lung carcinoma cell H128 was exposed to normoxia (air, 5% CO 2), hypoxia (5% O 2,5% CO 2,90% N 2) or anoxia (95% N 2,5% CO 2) conditions for 48 hours. The migration ability of the cells was assayed by wound healing methods. The invasiveness ability was determined with HABM-HEM model. The cells exposed to hypoxia were inoculated under skin in nude mice, and then the growth of the tumor and the rate of metastasis to lymph node or lung were observed. The expression of E-cadherin and β1-integrin on the cells were also assayed by flow cytometry. RESULTS: Compared with normoxic group, the invasiveness and migration in hypoxic group were increased. The rates of tumorgenesis and metastasis to lung in anoxic group were evidently decreased. The expression of E-cadherin was decreased, and the expression of β1-integrin was increased in hypoxic group. In anoxia group, the invasiveness, migration, the expression of E-cadherin and β1-integrin were all decreased. CONCLUSIONS: Moderate hypoxia down-regulated the expression of E-cadherin, up-regulated the expression of β1-integrin, and increased the invasiveness and metastasis of carcinoma cells. Serious hypoxia decreased the expression of adhesive molecules, and the proliferation, invasiveness and migration were also decreased.