Xiao Tan He Wei Decoction reverses MNNG-induced precancerous lesions of gastric carcinoma in vivo and vitro: Regulation of apoptosis through NF-κB pathway

Biomed Pharmacother. 2018 Dec:108:95-102. doi: 10.1016/j.biopha.2018.09.012. Epub 2018 Sep 12.

Abstract

In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.

Keywords: Chinese traditional medicine; Gastric cancer; Gastric precancerous lesions; NF-kB; Xian Tan He Wei Decoction.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / pathology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Hyperplasia
  • Methylnitronitrosoguanidine
  • NF-kappa B / metabolism*
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / pathology*
  • Rats, Wistar
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Drugs, Chinese Herbal
  • NF-kappa B
  • Methylnitronitrosoguanidine
  • Tetradecanoylphorbol Acetate