Effects of Hypoxia-inducible Factor-1α Silencing on Drug Resistance of Human Pancreatic Cancer Cell Line Patu8988/5-Fu

The present study aimed to investigate the mechanism and the possible approaches of solving drug resistance by silencing hypoxia-inducible factor-1 alpha of human pancreatic cancer cell line Patu8988/5-Fu cultured in hypoxia. The effective jamming fragment screened by RT-PCR for silencing HIF-1 alpha gene was transfected into pancreatic cancer cells Patu8988/5-Fu through lentivirus. RT-PCR results showed that the effective jamming fragments for HIP-1 alpha in lentivirus transfection was Wtl-mus-1202(C546). Combined MTT with JC-1 fluorescence staining flow cytometric analysis, the concentration of 200 mu mol/L CoCL2 for 8h was chosen to mimic hypoxia cell environment. The drug resistance significantly enhanced in response to hypoxia in Patu8988/5-Fu (p<0.05), and silence HIF-1 alpha could reverse the multidrug resistance(P<0.05). In the Patu8988/5-Fu cells, HIF-1 alpha and MDR1 significantly increased in response to hypoxia(p<0.05). The inhibition of HIP-1 alpha expression synergistically downregulated the expression of the MDR1 gene in Patu8988/5-Fu cells(p<0.05). HIF-1 alpha expression was positively correlated with the MDR1 expression(p<0.05). The upregulation of the HIF-1 alpha and MDR1 gene expression caused by hypoxia was related with the generation of multi-drug resistance of Patu8988/5-Fu, targeted silencing HIF-1 alpha may be a kind of way to reverse the chemotherapy drug resistance.