[Hypoxia-inducible factor-1 alpha dependent expression and significance of the related multidrug resistance genes induced by hypoxia in human hepatocarcinoma cell].
OBJECTIVE
To explore the mechanism of multidrug resistance of hepatocellular carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and multidrug resistance related genes.


METHODS
Human hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung resistance protein (LRP) gene at the mRNA and the protein levels in the above two groups were respectively analyzed by real-time fluorescent quantitative PCR and Western-blot technique.


RESULTS
In the hypoxia group, the expressions of mdr1, MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1 alpha. Also the increased expression of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid HIF-1 alpha/PCDNA3.


CONCLUSIONS
Resistance of hepatocellular carcinoma to chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the upregulation of the expression of the related multidrug resistance genes induced by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of hepatocellular carcinoma.
Zhu
Hong
H
Institute of Hepatobiliary Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. hong_jasmine2003@yahoo.com.cn
Chen
Xiao-ping
XP
Luo
Shun-feng
SF
Guan
Jian
J
Zhang
Wan-guang
WG
Zhang
Bi-xiang
BX
Wang
Hai-ping
HP
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014162:Transfection; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis / Q000235:genetics; D000099187:Major Vault Protein
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein