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    邓敏, 侯滨芬, 陈晓东. 大黄酚通过激活NLRP3炎症小体诱导胃癌细胞焦亡的机制研究[J]. 蚌埠医科大学学报, 2021, 46(8): 994-999. DOI: 10.13898/j.cnki.issn.1000-2200.2021.08.002
    引用本文: 邓敏, 侯滨芬, 陈晓东. 大黄酚通过激活NLRP3炎症小体诱导胃癌细胞焦亡的机制研究[J]. 蚌埠医科大学学报, 2021, 46(8): 994-999. DOI: 10.13898/j.cnki.issn.1000-2200.2021.08.002
    shu
    DENG Min, HOU Bin-fen, CHEN Xiao-dong. Study on the mechanism of chrysophanol inducing pyroptosis of gastric cancer cells by activating NLRP3 inflammasome[J]. Journal of Bengbu Medical University, 2021, 46(8): 994-999. DOI: 10.13898/j.cnki.issn.1000-2200.2021.08.002
    Citation: DENG Min, HOU Bin-fen, CHEN Xiao-dong. Study on the mechanism of chrysophanol inducing pyroptosis of gastric cancer cells by activating NLRP3 inflammasome[J]. Journal of Bengbu Medical University, 2021, 46(8): 994-999. DOI: 10.13898/j.cnki.issn.1000-2200.2021.08.002
    shu

    大黄酚通过激活NLRP3炎症小体诱导胃癌细胞焦亡的机制研究

    Study on the mechanism of chrysophanol inducing pyroptosis of gastric cancer cells by activating NLRP3 inflammasome

      摘要
    • 摘要:
      目的探索大黄酚诱导人胃癌细胞焦亡的作用及其可能的作用机制。
      方法不同浓度大黄酚（0、5、10 μmol/L）和NLRP3抑制剂、caspase-1抑制剂先后处理人胃癌MKN28细胞，CCK-8法、克隆形成实验、流式细胞术检测细胞焦亡；实时荧光定量PCR检测焦亡、NLRP3炎症小体相关蛋白的mRNA水平；Western blotting检测焦亡、NLRP3炎症小体的蛋白表达水平。
      结果不同浓度的大黄酚（0、5、10 μmol/L）作用于MKN28细胞后，均降低了细胞存活率（P < 0.01），并促进了细胞焦亡的发生（P < 0.01）。大黄酚呈剂量依赖性地上调胃癌MKN28细胞中NLRP3、caspase-1和白细胞介素-1β的mRNA以及蛋白表达水平（P < 0.01）。采用caspase-1抑制剂VX-765、NLPR3抑制剂MCC950抑制NLPR3炎症小体表达，可削弱大黄酚对细胞焦亡的诱导作用（P < 0.01）。
      结论大黄酚抑制人胃癌MKN28细胞增殖、促进LDH释放和caspase-1活性升高，诱导胃癌细胞焦亡，其作用机制与NLRP3/caspase-1通路密切相关。

       

      Abstract:
      ObjectiveTo explore the effects of chrysophanol on pyroptosis of human gastric cancer cells and its possible mechanism.
      MethodsThe human gastric cancer MKN28 cells were treated with chrysophanol at different concentrations(0, 5 and 10 μmol/L), NLRP3 inhibitor and caspase-1 inhibitor.The pyroptosis was detected using CCK-8 method, clone formation experiment and flow cytometry.The mRNA levels of pyroptosis and NLRP3 inflammasome-related proteins detected using real-time PCR.The protein expression levels of pyroptosis and NLRP3 inflammasome-related proteins were detected using Western blotting.
      ResultsThe different concentrations of chrysophanol(0, 5 and 10 μmol/L) could decrease the cell viability and promote the occurrence of pyroptosison of MKN28 cells(P < 0.01).In a dose-dependent manner, the chrysophanol increased the mRNA and protein expression levels of NLRP3, caspase-1 and IL-1β in MKN28 cells(P < 0.01).The caspase-1 inhibitor VX-765 and NLPR3 inhibitor MCC950 were used to inhibit the expression of NLPR3 inflammasome, which could reduce the induced effect of chrysophanol on pyrotosis(P < 0.01).
      ConclusionsThe chrysophanol can inhibit the proliferation, promote the release of LDH, increase the caspase-1 activity and induce the pyroptosis of gastric cancer MKN28 cells, and which might be related to the NLRP3/caspase-1 pathway.

       

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