The Expression And Significance Of HIF-1α, GLUT-1 And MMP-2 In Lung Carcinoma

Objective: To explore the changes of hypoxia-inducible factor 1α( HIF-1α) ,glucose transporter-1(GLUT-1),and matrix metalloproteinase-2(MMP-2) in hypoxic human lung adenocarcinoma cell line A549, and to investigate the effect of HIF-1αon the expression of GLUT-1 and MMP-2.Methods: The human lung adenocarcinoma A549 cells were cultured in normoxic and CoCl2-induced hypoxic conditions respectively.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.Results: There were some levels of mRNA and protein expression of HIF-1α, GLUT-1 and MMP-2 in A549 cells in normoxic condition.After hypoxia exposure, the mRNA expression increased time-dependentedly. Comparing with the normoxic group, the mRNA levels of HIF-1αand GLUT-1 in the hypoxic groups had significant difference (P<0.01). There was no dramatic increase in MMP-2 mRNA after 24-hour hypoxia. Long-term hypoxia (48h), however, significantly enhanced the mRNA level in contrast to the normoxic control(P<0.01). The protein expression of HIF-1αand GLUT-1 increased dramatically , and MMP-2 protein had no significant change under hypoxia.Conclusions:CoCl2 can up-regulate the expression of HIF-1α, GLUT-1 and MMP-2 in lung adenocarcinoma cell line A549 by inducing hypoxia. These hypoxia-mediated effects on them have the potential of enabling lung cancer cells to grow and migrate. GLUT-1 may be modulated by HIF-1αwhich plays important roles in tumor growth and progression. And HIF-1αprobably promotes invasion by regulating the expression of MMP-2 indirectly.