α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro
α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro
复制标题
DOI：
10.2147/ott.s221005
复制
发表时间：
2019-01-01
影响因子：
4
通讯作者：
Dong, Weiguo
中科院分区：
文献类型：
--
作者：
Liu, Yinghui;Lei, Hongbo;Dong, Weiguo
前言：胃癌在世界范围内仍是一种重要的癌症，常规化疗药物存在耐药性和细胞毒性的缺陷。阿尔法-赫德林已被发现对各种类型的人类癌症有一定的治疗效果。然而，关于对顺铂耐药的胃癌细胞具有生物活性的α-Hederin的研究还很有限。在本研究中，我们研究了α-Hederin对HGC27/DDP细胞的作用及其在体内和体外的可能机制。用细胞计数试剂盒-8定量检测细胞的增殖和活力。用Transwell侵袭实验和伤口愈合实验检测细胞的侵袭和迁移。用Hoechst 33258染色试剂盒和Annexin V-PE细胞凋亡试剂盒检测细胞凋亡率。用GSH检测试剂盒检测细胞内GSH水平。用DCFH-DA和JC-1试剂盒检测细胞内活性氧(ROS)水平和线粒体膜电位的变化。Western印迹法检测Apaf-1、AIF、Bax、Bcl2、CytC、Survivin、裂解caspase-3、裂解caspase-9、MMP9、MMP2的蛋白水平。结果：与对照组相比，α-Hederin能明显抑制HGC27/DDP细胞的增殖，并诱导明显的细胞凋亡，且呈剂量和时间依赖性。
Introduction: Gastric cancer remains an important cancer worldwide, and conventional chemotherapeutic drugs have the defects of drug resistance and cell toxicity. alpha-Hederin has been found to have certain therapeutic effects on various types of human cancers. However, studies on the alpha-hederin that exert biological activities on the cisplatin-resistant gastric cancer cells are limited. In this study, we evaluated the effects of alpha-hederin in HGC27/DDP and the potential mechanisms both in vivo and in vitro.Methods: HGC27/DDP cells were cultured in DMEM/F12 medium. Cell proliferation and viability were assessed quantitatively using Cell Counting Kit-8. Cell invasion and migration were detected by Transwell invasion assay and wound healing assay. Cell apoptosis was examined by employing Hoechst 33258 Staining Kit and an Annexin V-PE apoptosis kit. Intracellular GSH levels were examined by using a GSH Assay Kit. DCFH-DA and JC-1 Kit were used to detect levels of intracellular reactive oxygen species (ROS) and changes in mitochondrial membrane potential (Delta psi m). The protein levels of Apaf-1, AIF, Bax, Bcl-2, Cyt C, Survivin, cleaved caspase-3, cleaved caspase-9, MMP-9 and MMP-2 were detected by Western blot analysis. The effect of alpha-hederin in vivo was observed by xenograft tumor models in nude mice.Results: The alpha-hederin treatment significantly inhibited the proliferation in a dose- and time-dependent manner of HGC27/DDP and induced obvious apoptosis compared with the control group (P