title: Effects of hypoxia-inducible factor-1α silencing on drug resistance of human pancreatic cancer cell line Patu8988/5-Fu.
abstract: 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.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Yang
authors.forename: Bi-qing
authors.initials: BQ
authors.lastname: Song
authors.forename: Shu-Long
authors.initials: SL
authors.lastname: Dai
authors.forename: Kun-Xing
authors.initials: KX
authors.lastname: Yang
authors.lastname: Jin-Zhou
authors.forename: Kai-Wang
authors.initials: KW
authors.lastname: Shi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005472:Fluorouracil