Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer

Frontiers in Pharmacology

Xiangqing Liao¹  Weiqing Wu¹  Min Zhao²  Bending Tong²  Yingying Kou³ 

[1] Department of Health Management, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical College of Jinan University, Shenzhen, China;Department of Pharmacy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Hospital of Nanjing Medical University, Nanjing, China;GCP Office, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Hospital of Nanjing Medical University, Nanjing, China;

关键词: gastric cancer;    cisplatin;    berberine;    apoptosis;    PI3K/AKT/mTOR 2;   

DOI  :  10.3389/fphar.2020.616251

来源: DOAJ

【 摘 要 】

Gastric cancer is one of the most common malignancies ranks as the second leading cause of cancer-related mortality in the world. Cisplatin (DDP) is commonly used for gastric cancer treatment, whereas recurrence and metastasis are common because of intrinsic and acquired DDP-resistance. The aim of this study is to examine the effects of berberine on the DDP-resistance in gastric cancer and explore the underling mechanisms. In this study, we established the DDP-resistant gastric cancer cells, where the IC50 values of DDP in the BGC-823/DDP and SGC-7901/DDP were significantly higher than that in the corresponding parental cells. Berberine could concentration-dependently inhibited the cell viability of BGC-823 and SGC-7901 cells; while the inhibitory effects of berberine on the cell viability were largely attenuated in the DDP-resistant cells. Berberine pre-treatment significantly sensitized BGC-823/DDP and SGC-7901/DDP cells to DDP. Furthermore, berberine treatment concentration-dependently down-regulated the multidrug resistance-associated protein 1 and multi-drug resistance-1 protein levels in the BGC-823/DDP and SGC7901/DDP cells. Interestingly, the cell apoptosis of BGC-823/DDP and SGC-7901/DDP cells was significantly enhanced by co-treatment with berberine and DDP. The results from animals also showed that berberine treatment sensitized SGC-7901/DDP cells to DDP in vivo. Mechanistically, berberine significantly suppressed the PI3K/AKT/mTOR in the BGC-823/DDP and SGC-7901/DDP cells treated with DDP. In conclusion, we observed that berberine sensitizes gastric cancer cells to DDP. Further mechanistic findings suggested that berberine-mediated DDP-sensitivity may be associated with reduced expression of drug transporters (multi-drug resistance-1 and multidrug resistance-associated protein 1), enhanced apoptosis and repressed PI3K/AKT/mTOR signaling.

【 授权许可】

Unknown