Anti-angiogenic and anti-proliferative effects of inhibition of HIF-1α by p-HIF-1α RNAi in colorectal cancer

p-HIF-1α RNAi 抑制结直肠癌 HIF-1α 的抗血管生成和抗增殖作用

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作者:Yan-Yan Qiu, Song-Jiao Hu, Yi-Jie Bao, Bo Liang, Cui-Na Yan, Xiao-Jing Shi, Hui Yu, Yu Zou, Li-Rui Tang, Qing-Feng Tang, Wen Feng, Pei-Hao Yin

Abstract

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.

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