The drug resistance may be the consequence of the increased cell viability by HIF-1 in Pancreatic cancer cell
- The drug resistance may be the consequence of the increased cell viability by HIF-1 in Pancreatic c...
Departments of 2 Pathology and 4 Medical Microbiology, Ankara University, School of Medicine, Ankara, Turkey
3 Department of Medical Biology, Yüzüncü Yıl University, School of Medicine, Van, Turkey
Background and aims: Hypoxia-inducible factor-1 α (HIF-1 α) isan important factor in the adaptation of cells to hypoxic environments and signifiantlycontributes to the aggressiveness and chemoresistance of a number of different tumours. In this study, we aimed to investigate the effects of HIF-1α gene overexpressionin pancreatic cancer cell line (PancI) on cell survival and drug resistance. Materialsand Methods: For this purpose, HIF-1α cDNA was cloned into the pcDNA mammalianexpression vector. Sequentially HIF-1α ectopically overexpressed in PancI cell line andphenotypic changes including cell survive, and drug resistance were investigated. Cellsurvive, and drug resistance (doxorubicin) were tested with MTT assay. Colony formingassay was used as another test for the drug resistance analysis. Multiplex RT-PCR andwestern blot were utilized for the gene and protein expression analysis respectively.Results: Results showed that HIF-1α overexpression increases cell survival as muchas 40% in three days. However, doxorubicin decreased cell survival at the same ratein both cells overexpressing HIF-1α and not. Expression analysis of the Akt-1, Bax,mTOR, cIAPI, cIAPII, Bcl2 and XIAP showed that neither of the genes’ expressions waseffected by the HIF-1α overexpression. Conclusion: As a conclusion the results of thisstudy showed that HIF-1α increase the cell survival in PancI cell and doxorubicin mayact on the targets related to the cell survival.