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Apoptosis induction by p38 MAPK inhibitor in human colon cancer cells.

机译:p38 MAPK抑制剂在人结肠癌细胞中诱导凋亡。

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摘要

BACKGROUND/AIMS: The p38 mitogen-activated protein kinases (p38 MAPKs) function in a wide variety of signaling pathways. However, the role of p38s is cell type- and stimulus-dependent. The present study aimed to evaluate the effects of p38 MAPK inhibitor on human colon cancer cells. METHODOLOGY: The effect of p38 MAPK inhibitor, FR167653, on DLD-1 and SW480 was investigated related to cell proliferation, apoptosis induction and caspase activity. Additionally, the effect of FR167653 on colon cancer cell migration, MMPs production and ability to adhere to extracellular matrix was investigated. RESULTS: Inhibitor of p38 MAPK dose-dependently suppressed the proliferative activity of both cell lines, and increased the induction of cell apoptosis. The caspase-3, 8, and 9 activities were accompanied in the pathway. Neither cell migration, MMPs production, nor the ability to adhere extracellular matrix were affected by FR167653. CONCLUSIONS: Inhibitor of p38 MAPK suppressed the proliferation of colon cancer cells by induction of cell apoptosis through the caspase activation. The present results suggest the pro-oncogenic role ofp38 in colon cancer, and its inhibition would be a novel strategy for the prevention and treatment of colon cancer.
机译:背景/目的:p38促分裂原活化蛋白激酶(p38 MAPK)在多种信号通路中起作用。但是,p38s的作用是细胞类型和刺激依赖性的。本研究旨在评估p38 MAPK抑制剂对人结肠癌细胞的作用。方法:研究了p38 MAPK抑制剂FR167653对DLD-1和SW480的影响,该作用与细胞增殖,凋亡诱导和胱天蛋白酶活性有关。另外,研究了FR167653对结肠癌细胞迁移,MMP产生和粘附细胞外基质的能力的影响。结果:p38 MAPK抑制剂剂量依赖性地抑制了两种细胞系的增殖活性,并增加了对细胞凋亡的诱导。该途径伴随有caspase-3、8和9活性。 FR167653既不影响细胞迁移,MMP产生,也不粘附细胞外基质。结论:p38 MAPK抑制剂通过胱天蛋白酶激活诱导细胞凋亡,从而抑制了结肠癌细胞的增殖。目前的结果表明p38在结肠癌中的促癌作用,其抑制作用将是预防和治疗结肠癌的新策略。

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