A Preliminary Study On The Correlation Between Hif-1α And Gefitinib-resistant

ObjectiveHypoxia-inducible factor-1α(HIF-1α) is a transcriptional factor which is activated by hypoxia and associated with cell survival, proliferation and drug resistance.Recent studies have shown that gefitinib can circumvent the hypoxia-induced drug resistance via the regulation of HIF-1αexpression. Thus, we aim to study that the expression of HIF-1αmight be related to gefitinib-resistant.MethodsHuman lung cancer cell lines of A549 cells and gefitinib-resistant strains of A549/I cells were culture in vitro .These cells were divided into 4 groups: group A:A549 cells were incubated at normoxia condition; group B:gefitinib-resistant strains of A549/I cells were incubated at normoxia condition;group C:A549 cells were incubated at hypoxia condition(2.0%O2);group D:gefitinib-resistant strains of A549 / I cells were incubated at hypoxia condition(2.0%O2).The expressions of HIF-1αmRNA and protein levels were investigated by RT-PCR and Western blotting. ResultRT-PCR showed that the expression of HIF-1αmRNA in group B is 0.54±0.07 and in group A is 0.48±0.08 . There was no significant difference between group A and group B (P>0.05). The expression of HIF-1αmRNA in group C is 0.72±0.04and in group D is 0.94±0.09.There was no significant difference between group C and group D(P>0.05).The expression of HIF-1αprotein levels in group B is 0.54±0.07 which is much higher than group A .The expression of HIF-1αprotein levels in group C is 0.72±0.04 and in group D is 0.94±0.09.There was significant difference between group C and group D(P<0.05).It shows that the expression of HIF-1αprotein levels are different between A549 cells and A549/I cells in both normoxia and hypoxia condition.ConclusionHIF-1αis one of the key factors in the gefitinib-resistant, yet the prediction of HIF-1αand the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.