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首页> 外文期刊>Journal of Pharmacy and Pharmacology >Anticancer activity of tetrandrine tetrandrine by inducing pro‐death apoptosis and autophagy in human gastric cancer cells
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Anticancer activity of tetrandrine tetrandrine by inducing pro‐death apoptosis and autophagy in human gastric cancer cells

机译:通过在人胃癌细胞中诱导小脑凋亡和自噬的抗邻毒素Tetrandrine的抗癌活性

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摘要

Abstract Objectives To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. Methods The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh‐123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP ‐ LC 3 transfection. Key findings The results revealed that tetrandrine exhibits significant antitumour activity against gastric human cancer cell and the antigastric tumour activity was depended on inducing autophagy and apoptosis through upregulating the apoptosis‐related protein (cleaved PARP , cleaved caspase‐3 and cleaved caspase‐9) and autophagy‐related protein (Beclin‐1, LC 3‐ II and p62), and decreasing the phosphorylation of AKT / mTOR , PS 6K and P‐4 EBP 1. Adding the inhibitor of autophagy, 3‐ MA or Baf‐A1, increased the viability of tetrandrine ‐exposed gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by tetrandrine . Conclusions These results demonstrated that the antitumour effects of tetrandrine by inducing autophagy and apoptosis involving Akt/ mTOR pathway. Thus, tetrandrine may be a promising lead compound to be further developed in future for cancer therapy.
机译:摘要目的通过诱导人胃癌细胞的自噬和细胞凋亡,探讨北洲藻的抗肿瘤性质,探讨潜在的分子机制。方法通过MTT测定评估Tetrandrine的抗肿瘤活性。通过流式细胞术测量细胞凋亡和细胞形态学的微观检查。通过用RH-123染色来检测线粒体膜电位。通过GFP - LC 3转染通过透射电子显微镜观察监测自噬诱导。主要发现结果显示,Tetrandrine对胃癌细胞表现出显着的抗肿瘤活性,并且通过上调凋亡相关的蛋白(切割PARP,切割的Caspase-3和切割的Caspase-9)依赖于诱导自噬和凋亡的抗抗体肿瘤活性。与自噬相关的蛋白质(BECLIN-1,LC 3-II和P62),并降低AKT / mTOR,PS 6K和P-4 EBP的磷酸化1.加入自噬抑制剂,3- mA或BAF-A1增加四丁胺胃癌细胞的活力证实了自噬作用在Tetrandrine诱导的胃癌细胞死亡中发挥作用。结论这些结果表明,Tetrandrine通过诱导涉及Akt / mTOR途径的凋亡的抗腹毒性。因此,Tetrandrine可以是未来进一步发展的有前途的铅化合物,用于癌症治疗。

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  • 作者单位

    Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research;

    Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research;

    College of Basic MedicineChangchun University of Chinese MedicineChangchun China;

    Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research;

    Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research;

    College of Basic MedicineChangchun University of Chinese MedicineChangchun China;

    Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    apoptosis; autophagy; HGC ‐27; tetrandrine;

    机译:细胞凋亡;自噬;HGC -27;北洲;

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