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-1α gene was transfected into pancreatic cancer cells Patu8988/5-Fu through lentivirus. RT-PCR results showed that the effective jamming fragments for HIF-1α in lentivirus transfection was Wtl-mus-1202(C546). Combined MTT with JC-1 fluorescence staining flow cytometric analysis, the concentration of 200 μmol/L CoCl2 for 8 h 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-1α could reverse the multidrug resistance (P<0.05). In the Patu8988/5-Fu cells, HIF-1α and MDR1 significantly increased in response to hypoxia (p<0.05). The inhibition of HIF-1α expression synergistically downregulated the expression of the MDR1 gene in Patu8988/5-Fu cells (p<0.05). HIF-1α expression was positively correlated with the MDR1 expression (p<0.05). The upregulation of the HIF-1α and MDR1 gene expression caused by hypoxia was related with the generation of multi-drug resistance of Patu8988/5-Fu, targeted silencing HIF-1α may be a kind of way to reverse the chemotherapy drug resistance.