低氧诱导的小窝蛋白-1上调参与人肺腺癌细胞A549迁移和侵袭

 目的:探讨低氧诱导剂二氯化钴（CoCl2）对小窝蛋白-1（Cav-1）生成的调节作用及后者对人肺腺癌A549细胞迁移、侵袭的影响。方法:检测肺癌患者伴恶性胸水（MPE）和结核性胸膜炎患者胸水（TBPE）中Cav-1和缺氧诱导因子(HIF)-1α浓度，比较两者相关性；以CoCl2和（或）HIF-1α抑制剂YC-1作用于A549细胞ELISA法检测细胞上清Cav-1和HIF-1α浓度；分别采用细胞划痕实验及Transwell小室侵袭实验研究CoCl2刺激表达的Cav-1对A549细胞迁移和侵袭的影响。结果:MPE中Cav-1和HIF-1α浓度明显高于TBPE，两组患者胸水中Cav-1与HIF-1α均呈正相关。CoCl2浓度和时间依赖性诱导A549细胞Cav-1和HIF-1α生成，200 μmol/L或24 h达到峰值；浓度>200 μmol/L或作用时间超过24 h则呈现浓度或时间依赖性抑制。HIF-1α抑制剂YC-1浓度依赖性抑制HIF-1α和Cav-1生成。CoCl2浓度依赖性增强A549细胞迁移和侵袭，200 μmol/L作用最强；YC-1对上述过程产生抑制效应。结论: 肺癌患者胸腔积液中Cav-1浓度升高，低氧诱导Cav-1生成的变化可能参与了A549细胞迁移和侵袭，HIF-1α可能对Cav-1生成发挥影响。

Hypoxia-induced caveolin-1 up-regulation is involved in migration and in-vasion of lung adenocarcinoma A549 cells

AIM:To investigate the regulatory role of hypoxia mimic reagent cobalt chloride (CoCl2) on caveolin-1 (Cav-1) generation and the influence of Cav-1 on the abilities of migration and invasion of human lung adenocarcinoma A549 cells. METHODS:The concentrations of Cav-1 and hypoxia-inducible factor (HIF)-1α in pleural effusion of the patients with lung cancer (MPE) or tuberculous pleurisy (TBPE) were detected, and the correlation was also compared. A549 cells were treated with CoCl2 at different concentrations and time in the presence or absence of HIF-1α inhibitor YC-1. The concentrations of Cav-1 and HIF-1α in the cell supernatants were measured by ELISA. The effects of Cav-1 induced by CoCl2 on the migration and invasion of A549 cells were determined by scratch test and Transwell invasion trial, respectively. RESULTS:The levels of Cav-1 and HIF-1α in MPE were significantly higher than those in TBPE. There was a highly positive correlation between Cav-1 and HIF-1α levels in the pleural effusion. CoCl2 induced the generation of Cav-1 and HIF-1α in A549 cells in a concentration- and time-dependent manner, the peak occurred at 200 μmol/L or 24 h, while the concentration over 200 μmol/L or after treated over 24 h, a concentration- or time-dependent inhibition was observed. HIF-1α inhibitor YC-1 concentration-dependently inhibited the generation of HIF-1α and Cav-1 induced by CoCl2 in A549 cells. CoCl2 enhanced A549 cells migration and invasion, with 200 μmol/L played the strongest role, which were down-regulated significantly in the presence of YC-1. CONCLUSION: The alteration of hypoxia-induced Cav-1 generation might be involved in the migration and invasion of A549 cells. A possible role for HIF-1α is indicated in Cav-1 generation.