ABSTRACT
Dendrobium officinale is a herb in traditional Chinese medicine where D. officinale polysaccharides (DOP) are the main active ingredient. This study aimed at evaluating DOP efficiency at inhibiting 1-Methyl-2-nitro-1-nitrosoguanidine (MNNG) induced precancerous lesions of gastric cancer (PLGC) in rats through the Wnt/b-catenin pathway and analyzing the variations of serum endogenous metabolites. PLGC was established in male Sprague-Dawley (SD) rats by administering 150 µg/mL MNNG in drinking water for 7 months and giving 0.1 mL of 10% NaCl once weekly during the initial 20 weeks. Treatment with DOP inhibited the progress of PLGC through decreasing the expression of ß-catenin by immunohistochemical analysis. The futher study indicated DOP downregulated gene expression of Wnt2ß, Gsk3ß, PCNA, CyclinD1, and ß-catenin, as well as protein expression of Wnt2ß, PCNA, and ß-catenin. On the other hand, there were nine endogenous metabolites identified after the DOP treatment. Among these, the most significant one is betaine because of its strong antioxidant activity, leading to an anti-tumor effect. DOP can inhibit MNNG-induced PLGC models via regulating Wnt/ß-catenin pathway and by changing endogenous metabolites.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Dendrobium/chemistry , Gene Expression Regulation, Neoplastic , Polysaccharides/pharmacology , Precancerous Conditions/prevention & control , Stomach Neoplasms/prevention & control , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Betaine/blood , Cyclin D1/genetics , Cyclin D1/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Male , Metabolome/genetics , Methylnitronitrosoguanidine/toxicity , Plant Extracts/chemistry , Polysaccharides/isolation & purification , Precancerous Conditions/chemically induced , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Stomach Neoplasms/chemically induced , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Wnt Proteins/genetics , Wnt Proteins/metabolism , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.
