RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.
The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1α). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1α inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1α was achieved by HIF-1α-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1α and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1α expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1α further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1α could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.|Department of Radiology, Henan Cancer Hospital, Zhengzhou University, No.127 Dongming Road, Zhengzhou, 450008, China.
ChengShi
C
Chen
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China. contribution036@163.com.
Rong
R
Liu
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China. wang.jianhua@zs-hospital.sh.cn.
JianHua
J
Wang
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.
ZhiPing
Z
Yan
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.
Sheng
S
Qian
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.
Wei
W
Zhang
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D055785:Gene Knockdown Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A
Hepatocellular carcinoma; Hypoxia-inducible factor-1alpha; RNA interference; Vascular endothelial growth factor