Effect of hypoxia on HIF-1α, GLUT-1, and MMP-2 in human lung adenocarcinoma cells / 肿瘤

ABSTRACT

Objective: To explore the changes of hypoxia-inducible factor 1α(HIF-1α), glucose transporter protein-1(GLUT-1), and matrix metalloproteinase-2 (MMP-2) in hypoxic human lung adenocarcinoma A549 cells. Methods: The human lung adenocarcinoma A549 cells were cultured in normoxic and CoCl2-induced hypoxic conditions respectively. MTT assay was used to test the effect of hypoxia on the proliferation of lung cancer cells, and Transwell assay to determine the invasive capacity of hypoxic cells. Reverse transcription-polymerase chain reaction analyses (RT-PCR) was used to detect the mRNA expression of HIF-1α, GLUT-1 and MMP-2 under hypoxia. The protein levels of HIF-1α, GLUT-1, and MMP-2 were measured with immunohistochemical staining and western blot at different time points after hypoxia. Results: The proliferative and invasive capabilities of lung cancer cells increased under hypoxia condition. HIF-1α, GLUT-1, and MMP-2 were expressed at certain levels in A549 cells under normoxic condition. After hypoxia exposure, the mRNA and protein expression of the three proteins increased in a time-dependent manner. The difference was significant between hypoxia group and normal control group (P <0.05). Conclusion: Hypoxia induced by CoCl2 up-regulates the expression of HIF-1α, GLUT-1 and MMP-2 in lung adenocarcinoma A549 cells and stimulates the proliferation and metastasis of lung cancer cells, thus further promotes their tolerance to hypo-xia.