Effect of hypoxia on infiltration and migration of lung cancer cells and expression of MMP-2 and TIMP-2

Abstract

It has been known that different degrees of hypoxia can produce different effects on tumor. The study is to investigate the effect of hypoxia on the infiltration and migration of lung adenocarcinoma cells. Lung adenocarcinoma cells were exposed to normoxic (air, 5%O₂), hypoxic (1%O₂, 5%CO₂, 94%N₂) or anoxic (95%N₂, 5%CO₂) condition for 48 hours. The migration ability of the cells was assayed by wound healing methods. The infiltration ability was assayed by HABM-HEM model. The cells exposed to hypoxia were planted subcutaneously in nude mice, and the growth of cells and the rate of metastasis to lymph node or lung were observed. The levels of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase II (TIMP-2) in culture media were assayed by ELISA. Comparing with normoxia group, the infiltration, migration and metastasis of hypoxia group were increased significantly (P < 0.05) , as well as the level of MMP-2 (P < 0.01), and the TIMP-2 level was remarkably decreased (P < 0.05) . In anoxia group, the levels of MMP-2 and TIMP-2 were both significantly decreased (P < 0.01). Moderate hypoxia can up-regulate the expression of MMP-2, down-regulate the expression of TIMP-2, and increase the infiltration and migration of lung cancer cells. But serious hypoxia can decrease the expression of MMP-2 and TIMP-2, and inhibit the proliferation, infiltration and migration of lung cancer cells.