α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro

• Published in: OncoTargets and therapy 2019-01, Vol.12, p.8737-8750
• Main Authors: Liu, Yinghui, Lei, Hongbo, Ma, Jingjing, Deng, Huan, He, Pengzhan, Dong, Weiguo
• Format: Article
• Language: English
• Subjects: Original Research
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S221005

Gastric cancer remains an important cancer worldwide, and conventional chemotherapeutic drugs have the defects of drug resistance and cell toxicity. α-Hederin has been found to have certain therapeutic effects on various types of human cancers. However, studies on the α-hederin that exert biological activities on the cisplatin-resistant gastric cancer cells are limited. In this study, we evaluated the effects of α-hederin in HGC27/DDP and the potential mechanisms both in vivo and in vitro. 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 (∆Ψm). 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 α-hederin in vivo was observed by xenograft tumor models in nude mice. The α-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