title: Hypoxia-induced increases in A549/CDDP cell drug resistance are reversed             by RNA interference of HIF-1α expression.
abstract: This study aimed to investigate the effects of knocking down hypoxia-inducible             factor-1α (HIF-1α) through RNA interference on hypoxia-induced increases in drug             resistance in A549/CDDP cells, and to study the underlying mechanisms. A small             interfering RNA (siRNA) eukaryotic expression vector targeting HIF-1α was constructed             and transfected into A549/CDDP cells treated with hypoxia. The mRNA and protein             levels of HIF-1α, multidrug resistance-1 (MDR1), and multidrug resistance-associated             protein (MRP) were determined by reverse transcription polymerase chain reaction             (RT-PCR) and immunocytochemistry. Cell viability following treatment with cisplatin             was determined by MTT assay. Hypoxia increased the resistance of A549/CDDP cells             to cisplatin and this effect was reversed by the siRNA inhibition of HIF-1α expression.             Expression of HIF-1α siRNA also downregulated HIF-1α, MDR1 and MRP mRNA, and protein             expression in A549/CDDP cells treated with hypoxia (p<0.05). Hypoxia-induced             resistance of A549/CDDP cells to cisplatin is reversed by the siRNA inhibition             of HIF-1α expression. This effect may be mediated by a decreased expression of             MDR1 and MRP.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of South China, Hengyang 421001, PR China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Min
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Shuya
authors.initials: S
authors.lastname: He
authors.forename: Shenggang
authors.initials: S
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002945:Cisplatin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering