首页|Overexpression of Dickkopf-3 induces apoptosis through mitochondrial pathway in human colon cancer

Overexpression of Dickkopf-3 induces apoptosis through mitochondrial pathway in human colon cancer

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AIM:To investigate the mechanisms of the biological roles of Dickkopf-3 (Dkk-3) in cell invasion,survival and apoptosis in colon cancer cells.METHODS:Three human colon cancer cell lines,i.e.,HT-29,LoVo and SW480,were used.Overexpression of Dkk-3 induced by pEGFP-N1-Dkk-3-GFP plasmid in LoVo cells was performed using Lipofectamine 2000reagent.Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of Dkk-3,respectively.Cell proliferation assay,cell cycle analysis,hoechst 33258 assay and Matrigel invasion assay were performed on Dkk-3 overexpressing transfectants.RESULTS:The mRNA and protein expressions of Dkk-3 in HT-29 (mRNA:0.06 ± 0.02,protein:0.06 ±0.01) and LoVo (mRNA:0.07 ± 0.02,protein:0.07 ±0.02) cells were significantly lower than that in SW480 cells (mRNA:0.92 ± 0.04,protein:0.69 ± 0.13; all P < 0.05),and the greatest levels of invasiveness was in LoVo cells.Dkk-3 overexpression inhibited the proliferation and invasion of LoVo cells and induced cell cycle arrest at G0/G1 phase and subsequent apoptosis,as indicated by increased chromatin condensation and fragments,upregulated Bax and cytochrome c protein,downregulated survivin and Bcl-2 protein,and the activation of caspase-3 and caspase-9.Furthermore,Dkk-3 overexpression reduced the accumulation of cytosolic fraction of β-catenin.CONCLUSION:Dkk-3 overexpression induced apoptosis in human colon cancer possibly through the mitochondrial pathway.Dkk-3 may be involved in the Wnt/β-catenin signaling pathways in colon cancer.

Dickkopf-3OverexpressionInvasionApotosisColon cancerMitochondria

Zi-Rong Yang、Wei-Guo Dong、Xiao-Fei Lei、Meng Liu、Qi-Sheng Liu

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Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China

Fundamental Research Funds for the Central Universities of China

20103020101000197

2012

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子:1.001
ISSN:1007-9327
年,卷(期):2012.18(14)
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