Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells.

Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells.
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冬凌草甲素剂量依赖性调节胃癌细胞的细胞衰老和凋亡

DOI:
10.1155/2021/5023536
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发表时间:
2021
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Chen Z
Chen Z
中科院分区:
其他
文献类型:
--
作者:
Wang Y;Lv H;Dai C;Wang X;Yin Y;Chen Z

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胃癌(GC)是致死率位居第四的癌症。目前缺乏有效的治疗方法,而且我们对其发病机制了解甚少。源自中草药冬凌草的冬凌草甲素具有多种抗癌活性。然而,冬凌草甲素对人胃癌的剂量依赖性效应仍不明确。在此,我们发现冬凌草甲素以时间和剂量依赖的方式抑制胃癌细胞生长。低剂量冬凌草甲素通过抑制c-Myc-AP4通路并增强p53-p21信号传导,诱导胃癌细胞周期阻滞于G0/G1期并引发细胞衰老。AP4过表达部分抵消了冬凌草甲素诱导的胃癌细胞衰老。高剂量冬凌草甲素诱导细胞凋亡和自噬,自噬抑制剂巴弗洛霉素A1(BafA1)可减弱冬凌草甲素诱导的细胞凋亡。总之,这些研究结果表明,不同剂量的冬凌草甲素可调节胃癌细胞的衰老和凋亡,因此冬凌草甲素可能对胃癌治疗有益。
Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC remain unclear. Here, we found that oridonin inhibited GC cell growth in a time- and dose-dependent manner. Low-dose oridonin induced GC cell cycle arrest at G0/G1 and cell senescence by suppressing the c-Myc-AP4 pathway and enhancing p53-p21 signaling. AP4 overexpression partly abrogated the oridonin-induced senescence of GC cells. High-dose oridonin induced apoptosis and autophagy, with the autophagy inhibitor BafA1 attenuating oridonin-induced apoptosis. Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC.
冬凌草甲素通过增加结直肠癌细胞中过氧化氢和谷胱甘肽的消耗来诱导细胞凋亡和衰老
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