Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis.

The hedgehog (Hh) signaling pathway is vital to vertebrate development, the homeostatic process and tumorigenesis. Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, which in turn promotes cancer metastasis and invasion. Resveratrol is a natural polyphenolic compound found in grapes, a variety of berries, peanuts and other plants. Numerous studies have demonstrated that the Hh signaling pathway is able to regulate the EMT, and that resveratrol can suppress carcinoma invasion and metastasis. In addition, certain studies have indicated that resveratrol can inhibit the Hh signaling pathway and EMT in cancers other than gastric cancer. The purpose of the present study was to investigate the inhibitory effect of resveratrol on the Hh signaling pathway and EMT in gastric cancer in vitro. Gastric cancer SGC-7901 cells were treated with resveratrol or cyclopamine at different concentrations. The viability of the cells was assessed using an MTT assay. The expression of Gli-1, a key component of the Hh signaling pathway, and Snail, E-cadherin and N-cadherin, key components of EMT, was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The invasion and metastasis of the cells were observed by performing a cell scratch test. The RT-PCR and western blotting showed a decrease in Gli-1, Snail and N-cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared with the control group, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine. The MTT assay indicated that the viability of the SGC-7901 cells was significantly decreased in a concentration-dependent manner following resveratrol and cyclopamine treatment. The cell scratch test showed slower cell invasion and metastasis in the resveratrol and cyclopamine groups. These findings indicated that resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro.

Homocysteine promotes intestinal fibrosis in rats with trinitrobenzene sulfonic acid-induced colitis.

BACKGROUND AND AIM: Previous studies have revealed significantly increased levels of plasma and mucosal homocysteine (Hcy) in patients with Crohn's disease (CD); however, whether Hcy is involved in intestinal fibrosis of CD remains unclear. This study aimed to investigate the effects of Hcy on intestinal fibrosis in TNBS/ethanol-induced colitis and to elucidate its potential mechanisms. METHODS: Sprague-Dawley rats were divided into 4 groups: normal control, normal + Hcy injection, TNBS model and TNBS model + Hcy injection. Hyperhomocysteinemia was induced by subcutaneous injection of Hcy. DAI, CMDI and HI were calculated to evaluate the severity of colitis. Masson trichrome staining was performed to assess the severity of fibrosis. The plasma and mucosal levels of Hcy were measured by HPLC-FD. The levels of IL-1ß, IL-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III in the colon were determined by ELISA, and the mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 were detected by RT-PCR. RESULTS: Hcy was found to increase the scores of DAI, CMDI and HI; levels of IL-1ß, Il-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III; and mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 in colonic tissue of rats with TNBS/ethanol-induced colitis. CONCLUSIONS: Hcy promotes intestinal fibrosis in rats with TNBS/ethanol-induced colitis, the underlying mechanisms of which may be attributed to its effects of increasing inflammatory damage, promoting the expression of profibrogenic cytokines and influencing MMPs/TIMPs balance.

Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism.

OBJECTIVE: To investigate the effect of homocysteine (Hcy) on intestinal permeability in rats with TNBS/ethanol-induced colitis and elucidate its mechanism. METHODS: Sprague-Dawley rats were divided into four groups: normal, normal + Hcy injection, TNBS model, and TNBS model + Hcy injection. Experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol; rats were injected subcutaneously with Hcy from the first day after the induction of experimental colitis on 30 consecutive days. To determine the severity of colitis, the disease activity index (DAI) was evaluated; colon tissues were collected for the detection of the activity of myeloperoxidase (MPO) and the contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, and MMP-9. Intestinal epithelial permeability was assessed with Evans blue (EB) dye. The levels of Hcy in plasma and colon mucosa were measured by high-performance liquid chromatography-fluorescence detection (HPLC-FD). RESULTS: Compared with the normal group, the DAI scoring and MPO activity, contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, MMP-9 in the colon and EB in the small intestine were significantly increased in the TNBS group (P < 0.01). Compared with the TNBS model group, the DAI scoring, plasma and colonic mucosa Hcy levels, MPO activity and contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, MMP-9 in colon and EB in small intestine were significantly increased in the TNBS-induced colitis rats with simultaneous Hcy injection (P < 0.01). CONCLUSION: Hcy can increase intestinal permeability and aggravate inflammatory damage in rats with TNBS-induced colitis, the underlying mechanisms of which may be attributed to its effects of promoting the expression of MMP-2 and MMP-9, leading to injury of the intestinal barrier.

Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.