Anti-angiogenic and anti-proliferative effects of inhibition of HIF-1α by p-HIF-1α RNAi in colorectal cancer.
The aim of this study was to construct an RNA-interference plasmid (p-HIF-1α RNAi) targeting the human HIF-1α gene and assess its effects on HIF-1α expression and its anti-tumour functions in vitro. p-HIF-1α RNAi was constructed and confirmed by polymerase chain reaction (PCR) and DNA sequencing. Reverse transcriptase PCR (RT-PCR) and western blot were performed to detect HIF-1α expression in HCT116 cells following transfection of p-HIF-1α RNAi and p-control. The anti-tumour effects and mechanism of action of p-HIF-1α RNAi in HCT116 cells were further investigated. p-HIF-1α RNAi significantly inhibited HIF-1α expression in the HCT116 cell line. p-HIF-1α RNAi inhibited cell viability and reduced VEGF but not bFGF expression in the supernatant of HCT116 cells, down-regulated b-catenin and VEGF expression, and altered β-catenin location in the HCT116 cell nucleus. The plasmid p-HIF-1α RNAi can effectively and specifically inhibit HIF-1α expression, inhibit cell proliferation, and alter the expression of key components in the Wnt/β-catenin signaling pathway. Thus, p-HIF-1α RNAi is a novel and extremely promising therapeutic inhibitor of HIF-1α.
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Yan-Yan
YY
Qiu
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Song-Jiao
SJ
Hu
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Yi-Jie
YJ
Bao
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Bo
B
Liang
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Cui-Na
CN
Yan
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Xiao-Jing
XJ
Shi
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Hui
H
Yu
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Yu
Y
Zou
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Li-Rui
LR
Tang
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Qing-Feng
QF
Tang
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Wen
W
Feng
Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Pei-Hao
PH
Yin
D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C495270:CTNNB1 protein, human; D017077:Culture Media, Conditioned; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2
Colorectal cancer; HIF-1α; RNAi; anti-angiogenic; anti-proliferative