Min Fu1, Yanju Liu1, Huanbo Cheng1, Kang Xu2, Guangzhong Wang3. 1. Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. 2. Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: kangxu05@hbtcm.edu.cn. 3. Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: wgzhong4067@sina.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch (CC) and Zingiber officinale Roscoe (dried ginger; DG) are traditional Chinese medicines. CC can dry dampness, relieve fire and detoxify, and is used to treat gastritis, gastric ulcer, colitis. DG can warm spleen and stomach for dispelling cold, used for the treatment of spleen and stomach deficiency. Both CC and DG are widely used to treat gastrointestinal diseases. CC-DG herb medicine combination originates from Huanglian decoction and Pinellia xiexin decoction in "Shanghan Lun" to comfort the stomach and intestines. CC and DG are used for the treatment of nausea and choking diaphragm which highly associated with gastric cancer clinically in ancient time. AIM OF THE STUDY: This study aimed to investigate the effects and underlying molecular mechanisms of CC-DG combination on gastric cancer. MATERIALS AND METHODS: The CC-DG extract was subjected to HPLC analysis. Viability (MTT) and cytotoxicity (CCK8) assays were performed using the SGC7901 and MFC cells. Cell cycle and apoptosis were measured by flow cytometry. The mRNA expression levels were measured by RT-PCR. In vivo anti-tumor activity of CC-DG was assessed in a tumor xenograft model. RESULTS: Twelve different proportions of CC-DG were tested for inhibitory effects on gastric cancer cells; CC-DG ratio 1:1 was found most effective. CC-DG administration significantly reduced the cell proliferation, migration, and colony formation, while increased cell apoptosis compared with the control group. CC-DG regulated differentially expressed genes in SGC7901 cells were subjected to pathway enrichment analysis. CC-DG significantly inhibited the cell glucose metabolism, downregulated the expression of LDHA and SLC2A1 genes, and changed the expression of other related genes including ME2, LDHD, LDHB, HIF1A, PKM, Pcx, and Got1. In addition, CC-DG suppressed tumorigenesis and inhibited MKI67 expression in the tumor xenograft model. CONCLUSIONS: CC-DG inhibited the proliferation, migration, invasion of SGC7901/MFC gastric cells, and in turn, suppressed tumorigenesis by regulating glucose metabolism through regulation of LDHA and SLC2A1 genes.
ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch (CC) and Zingiber officinale Roscoe (dried ginger; DG) are traditional Chinese medicines. CC can dry dampness, relieve fire and detoxify, and is used to treat gastritis, gastric ulcer, colitis. DG can warm spleen and stomach for dispelling cold, used for the treatment of spleen and stomach deficiency. Both CC and DG are widely used to treat gastrointestinal diseases. CC-DG herb medicine combination originates from Huanglian decoction and Pinellia xiexin decoction in "Shanghan Lun" to comfort the stomach and intestines. CC and DG are used for the treatment of nausea and choking diaphragm which highly associated with gastric cancer clinically in ancient time. AIM OF THE STUDY: This study aimed to investigate the effects and underlying molecular mechanisms of CC-DG combination on gastric cancer. MATERIALS AND METHODS: The CC-DG extract was subjected to HPLC analysis. Viability (MTT) and cytotoxicity (CCK8) assays were performed using the SGC7901 and MFC cells. Cell cycle and apoptosis were measured by flow cytometry. The mRNA expression levels were measured by RT-PCR. In vivo anti-tumor activity of CC-DG was assessed in a tumor xenograft model. RESULTS: Twelve different proportions of CC-DG were tested for inhibitory effects on gastric cancer cells; CC-DG ratio 1:1 was found most effective. CC-DG administration significantly reduced the cell proliferation, migration, and colony formation, while increased cell apoptosis compared with the control group. CC-DG regulated differentially expressed genes in SGC7901 cells were subjected to pathway enrichment analysis. CC-DG significantly inhibited the cell glucose metabolism, downregulated the expression of LDHA and SLC2A1 genes, and changed the expression of other related genes including ME2, LDHD, LDHB, HIF1A, PKM, Pcx, and Got1. In addition, CC-DG suppressed tumorigenesis and inhibited MKI67 expression in the tumor xenograft model. CONCLUSIONS: CC-DG inhibited the proliferation, migration, invasion of SGC7901/MFC gastric cells, and in turn, suppressed tumorigenesis by regulating glucose metabolism through regulation of LDHA and SLC2A1 genes.