Hypoxia-Inducible Factor 1 Promoter-Induced JAB1 Overexpression Enhances Chemotherapeutic Sensitivity of Lung Cancer Cell Line A549 in an Anoxic Environment

The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it isnecessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targetingand inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study,a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter wasconstructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drugcis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA andprotein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1.The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation beingarrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HREJAB1significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion,JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer.