Asian Pacific Journal of Cancer Prevention

  • 제16권6호
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  • Pages.2569-2574
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  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Cobalt Chloride Induces Necroptosis in Human Colon Cancer HT-29 Cells

  • Wang, Hai-Yu (Department of General Surgery, Zhongshan hospital, Fudan University) ;
  • Zhang, Bo (Department of General Surgery, Zhongshan hospital, Fudan University)
  • 발행 : 2015.04.03
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초록

Necroptosis, also known as "programmed necrosis", has emerged as a critical factor in a variety of pathological and physiological processes and is considered a cell type-specific tightly regulated process with mechanisms that may vary rather greatly due to the change of cell line. Here we used HT-29, a human colon cancer cell line, to establish a necroptosis model and elucidate associated mechanisms. We discovered that cobalt chloride, a reagent that could induce hypoxia-inducible $factor-1{\alpha}(HIF1{\alpha})$ expression and therefore mimic the hypoxic microenvironment of tumor tissue in some aspects induces necroptosis in HT-29 cells when caspase activity is compromised. On the other hand, apoptosis appears to be the predominant death form when caspases are functioning normally. HT-29 cells demonstrated significantly increased RIPK1, RIPK3 and MLKL expression in response to cobalt chloride plus z-VAD treatment, which was accompanied by drastically increased $IL1{\alpha}$ and IL6 expression, substantiating the notion that necrosis can induce profound immune reactions. The RIPK1 kinase inhibitor necrostatin-1 and the ROS scavenger NAC each could prevent necrosis in HT-29 cells and the efficiency was enhanced by combined treatment. Thus by building up a necroptosis model in human colon cancer cells, we uncovered that mechanically RIP kinases collaborate with ROS during necrosis promoted by cobalt chloride plus z-VAD, which leads to inflammation. Necroptosis may present a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death.

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참고문헌

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피인용 문헌

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  2. Cell Death Conversion under Hypoxic Condition in Tumor Development and Therapy vol.16, pp.10, 2015, https://doi.org/10.3390/ijms161025536