Salvianolic acid B suppresses EMT and apoptosis to lessen drug resistance through AKT/mTOR in gastric cancer cells

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ORIGINAL ARTICLE

Salvianolic acid B suppresses EMT and apoptosis to lessen drug resistance through AKT/mTOR in gastric cancer cells Jie Wang . Yingze Ma . Min Guo . Haixia Yang . Xiaohui Guan

Received: 4 August 2020 / Accepted: 4 November 2020 Ó Springer Nature B.V. 2020

Western blot. The results demonstrated that Sal-B acted alone or in synergy with DDP to reduce cell viabilities, initiate ROS generation, promote cell apoptosis, as well as decrease migration, invasion and EMT in AGS and AGS/DDP cells. AKT activator and mTOR activator significantly reversed the above effects of Sal-B. Collectively, Sal-B regulated proliferation, EMT and apoptosis to reduce the resistance to DDP via AKT/mTOR pathway in DDP-resistant gastric cancer cells. Sal-B could be a potential antidrug resistance agent to chemotherapy in gastric cancer.

Abstract The drug resistance of tumor cells greatly reduces the efficacy of chemotherapy drugs in gastric cancer. Salvianolic acid B (Sal-B) is considered as a chemopreventive agent which suppresses oxidative stress and apoptosis. Therefore, the study aims to clarify the mechanism of Sal-B in drug-resistant gastric cancer cells. CCK8 assay analyzed cell viabilities after GES1, AGS and AGS/DDP cells were respectively treated by Sal-B of different concentration or after AGS/DDP cells were disposed by cisplatin (DDP) in different concentration. The colony formation, ROS generation, apoptosis, migration, invasion and EMT marker proteins were respectively analyzed through formation assay, ROS kits, TUNNEL staining, Wound healing, Transwell assays and

Keywords Salvianolic acid B  Drug resistance  Cisplatin  Gastric cancer  AKT  DDR

J. Wang Department of Traditional Chinese Medicine, Affiliated Hospital of Beihua University, Jilin 132000, China

Introduction

Y. Ma  X. Guan Gastroenterology Department, Affiliated Hospital of Beihua University, Jilin 132000, China M. Guo Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, China H. Yang (&) Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Haixia Yang No. 157 West Five Road, Xi’an 710004, Shaanxi, China e-mail: [email protected]

Gastric cancer is one of the most common malignant tumors seriously threating people’s health and life, with higher incidence rate (Zhang and Fan 2010). Surgery and chemotherapy are still the main methods for clinical treatment of gastric cancer. However, the drug resistance of tumor cells greatly weakens the efficacy of chemotherapy drugs, leading to the treatment failure in most patients (Zhang and Fan 2007). Therefore, the research and development of new reversal agents against tumor drug resistance are the

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Cytotechnology

key to improve the efficacy of chemotherapy drugs and prolong the survival of patients. The symptoms of gastric cancer belong to the categories of Traditional Chinese medicine (TCM), such as epigastric pain, nausea, diaphragm choking, and so on. Weakness of spleen an