Tanshinone I attenuates gastric precancerous lesions by inhibiting epithelial mesenchymal transition through the p38/STAT3 pathway

  • Int Immunopharmacol. 2023 Sep 10;124(Pt A):110902. doi: 10.1016/j.intimp.2023.110902.
Dan Liang  1 ,  Shiyun Tang  1 ,  Lu Liu  2 ,  Maoyuan Zhao  1 ,  Xiao Ma  2 ,  Yanling Zhao  3 ,  Caifei Shen  4 ,  Qingsong Liu  5 ,  Jianyuan Tang  6 ,  Jinhao Zeng  7 ,  Nianzhi Chen  8
Affiliations
  • 1. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 2. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 3. Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
  • 4. Department of Endoscopy Center, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 5. Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 6. TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: [email protected].
  • 7. Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: [email protected].
  • 8. State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 37699302 DOI: 10.1016/j.intimp.2023.110902
Abstract

Background: Gastric precancerous lesions (GPLs) are omens for gastric Cancer (GC), which developing with a series of pathological changes of gastric mucosa. Reversing epithelial-mesenchymal transition (EMT) in gastric mucosa is the main approach to restrain GPLs from evolving into Cancer. Tanshinone I (Tan-I), the active ingredients of traditional Chinese herb Salvia miltiorrhiza, has exhibited Anticancer effect.

Purpose: To investigate the effect and mechanism of Tan-I in intervening GPLs, and provide a new therapeutic strategy for prevention of GC.

Methods: Gastric mucosal epithelial cells were treated with the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to construct MNNG-induced cell (MC cell) of gastric mucosa that undergoing EMT process. Then, this study explored the effect and mechanism of Tan-I in vitro. Subsequently, this study constructed GPL mice to clarify the exact efficacy and mechanism of Tan-I on GPLs.

Results: Tan-I inhibited MC cell proliferation, invasion and migration. Simultaneously, the aberrant expression of E-cadherin and N-Cadherin were reversed. Tan-I attenuated inflammation by reducing the release of nitric oxide, TNFα and IL-1β. Tan-I reversed the EMT and inflammatory processes by regulating p38 and STAT3.

Conclusion: This study showed that Tan-I inhibited the progression of GPLs by reversing the EMT process and reducing inflammation by restraining the p38/STAT3 signaling pathway.

Keywords
Epithelial-mesenchymal transition; Gastric cancer; Gastric precancerous lesions; Tanshinone I; p38/STAT3.
Products