Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-kappa B pathway
文献类型：期刊论文
| 作者 | Su, Kexin1; Yao, Xuan1,2; Guo, Chenxu3; Qian, Chunmei1; Wang, Yiying1; Ma, Xiaoqi1; Wang, Xiaoyu1,4; Yang, Yifu1 |
| 刊名 | CHEMICO-BIOLOGICAL INTERACTIONS
 |
| 出版日期 | 2023-07-01 |
| 卷号 | 379页码:12 |
| ISSN号 | 0009-2797 |
| 关键词 | Solasodine Gastric cancer Claudin-2 AMPK EMT |
| DOI | 10.1016/j.cbi.2023.110520 |
| 通讯作者 | Wang, Xiaoyu(0000002733@shutcm.edu.cn) ; Yang, Yifu(0000002402@shutcm.edu.cn) |
| 英文摘要 | Gastric cancer (GC) is one of the most common malignancies, and it has become the third most common ma-lignant tumour in the world. Targeting metastasis has also become a key and difficult point in the treatment of GC. Solasodine is an active ingredient isolated from Solanum nigrum L. for the treatment of various cancers, such as breast cancer, pancreatic cancer and lung cancer. In the present study, we investigated the role and mecha-nism of solasodine in inhibiting GC. In vitro, we found that solasodine not only promoted cell death but also inhibited the migration and invasion of HGC27 and AGS cells. Solasodine regulated epithelial-mesenchymal transition (EMT) and reduced the expression of claudin-2 (CLDN2). Moreover, overexpression of CLDN2 inhibited the prometastatic phenotype and EMT of GC, and solasodine recovered this phenotype. Furthermore, the knockdown of CLDN2 had the opposite effect. We also found that the AMPK activators metformin and AICAR activated phosphorylation of AMPK and downregulated the expression of RhoA and CLDN2, indicating that AMPK was the upstream regulator of CLDN2. Solasodine could also activate AMP-activated protein kinase (AMPK) and inhibit the phosphorylation of STAT3 and the nuclear translocation of NF-kappa B. Therefore, solasodine may have prevented EMT by modulating the AMPK/STAT3/NF-kappa B/CLDN2 signalling pathway. In vivo, we established a xenograft model to investigate the phosphorylation of AMPK and the expression of CLDN2 from tumour tissues, and we found that solasodine inhibited tumour growth through AMPK-CLDN2 pathway. To sum up, solasodine prevented EMT by modulating the AMPK/STAT3/NF-kappa B/CLDN2 signalling pathway, becoming a new solution for inhibiting GC metastasis. |
| WOS关键词 | ANTITUMOR-ACTIVITY ; COLORECTAL-CANCER |
| 资助项目 | State Key Laboratory of Drug Research[SIMM2205KF-16] ; budgetary Foundation of Shanghai University of Traditional Chinese Medicine[2021LK039] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| 出版者 | ELSEVIER IRELAND LTD |
| WOS记录号 | WOS:001000906900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306659]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Xiaoyu; Yang, Yifu |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China 2.Shanghai Jingxin Biopharmaceut Co Ltd, Shanghai 201203, Peoples R China 3.Eastern Hepatobiliary Surg Hosp, Shanghai 201805, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Kexin,Yao, Xuan,Guo, Chenxu,et al. Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-kappa B pathway[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2023,379:12. |
| APA | Su, Kexin.,Yao, Xuan.,Guo, Chenxu.,Qian, Chunmei.,Wang, Yiying.,...&Yang, Yifu.(2023).Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-kappa B pathway.CHEMICO-BIOLOGICAL INTERACTIONS,379,12. |
| MLA | Su, Kexin,et al."Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-kappa B pathway".CHEMICO-BIOLOGICAL INTERACTIONS 379(2023):12. |
入库方式： OAI收割
来源：上海药物研究所
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