Apatinib regulates the growth of gastric cancer cells by modulating apoptosis and autophagy
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ORIGINAL ARTICLE
Apatinib regulates the growth of gastric cancer cells by modulating apoptosis and autophagy Xu Liu 1 & Qiaoyu Zheng 1 & Qiongfang Yu 1,2 & Yan Hu 3 & Yanmin Cheng 1 & Zhaozhao Shao 1,2 & Li Chen 1,2 & Wenjie Ding 1,2 & Dian Gao 1 Received: 15 May 2020 / Accepted: 5 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Apatinib is a novel, highly selective small-molecule inhibitor of the tyrosine kinase VEGFR-2. Although its safety and efficacy in the treatment of advanced gastric cancer (GC) and other solid tumors have been confirmed, the precise molecular mechanism underlying its efficacy remains unclear. The purpose of this study was to investigate the mechanism by which apatinib regulates the biological functions of GC cells in vitro. The CCK-8 assay was used to detect the inhibitory effect of apatinib at different concentrations on the proliferation of SGC7901 and MKN45 human GC cells. The effects of apatinib on apoptosis, autophagy, and cell cycle-related genes in SGC7901 and MKN45 cells were detected by Western blotting and real-time quantitative PCR (RT-qPCR). JC-1 staining, flow cytometry, Hoechst 33342 staining, dansylcadaverine (MDC) staining, and Transwell assays were used to detect the effects of apatinib on apoptosis, the cell cycle, autophagy, and invasion and migration capacities, respectively, in SGC7901 and MKN45 cells. The inhibitory effect of apatinib on the proliferation of GC cells was dependent on concentration. Apatinib significantly promoted apoptosis and autophagy. It also altered the cell cycle distribution and inhibited the invasion and migration of GC cells. In general, apatinib inhibited the proliferation of GC cells by promoting apoptosis and autophagy, regulating the cell cycle and inhibiting the invasion and migration capacities of GC cells. Keywords Apatinib . Gastric cancer . Proliferation . Apoptosis . Autophagy
Introduction Gastric cancer (GC) remains a main cause of cancer-related death, although the incidence of GC has decreased in recent years (Torre et al., 2015). The current treatment for GC is surgery supplemented by chemotherapy, radiation therapy, and immunotherapy. Although recent advances in surgery and chemotherapy have been made, patients with advanced GC still have a higher recurrence rate after undergoing adjuvant therapy, and their prognosis remains very poor (Wagner et al., 2010; Petrioli et al., 2015). In China, an estimated * Dian Gao [email protected] 1
Department of Pathogen Biology and Immunology, Medical College of Nanchang University, Nanchang 330006, China
2
Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
3
Clinical Laboratory, Wuhan Pulmonary Hospital, Wuhan 430030, China
400,000 new cases of GC occur each year, accounting for 43% of total cases worldwide. The 5-year survival rate of patients undergoing existing treatments is only 20% (Ferlay et al., 2010). The emergence of resistance during cancer treatment remains a barrier t
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