Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway.

BACKGROUND: Gastric cancer is one of the most common and deadly malignancies worldwide. Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-fluorouracil (5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis. However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis, though its effect on gastric cancer remains unknown. AIM: To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu. METHODS: Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede. Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin (mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection. RESULTS: Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistance-related proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased, respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change. CONCLUSION: The natural extract of Cycas revoluta Thunb. effectively inhibited gastric cancer cell growth and enhanced the anti-cancer effect of 5-Fu through the AKT-mTOR pathway.

A randomized, double-blind, placebo-controlled trial to assess the essentiality of acid inhibitors for abdominal pain after gastroscopic mucosal biopsy.

BACKGROUND/AIMS: Gastroscopy and gastroscopic mucosal biopsy techniques have become increasingly used as of late for evaluating symptoms presumed to be originated in the upper gastrointestinal tract. Patients often complain however of abdominal pain post-gastroscopic mucosal biopsy, and this study aimed to explore the necessity of acid inhibitors when abdominal pain worsened. MATERIALS AND METHODS: In this randomized, double-blinded, placebo-controlled study, we screened 272 participants, and ultimately enrolled 200 into the study. These 200 participants were randomly assigned in a 1:1 ratio to receive acid inhibitors (esomeprazole, treatment group, n=100; dose,20 mg/d) or matched placebo (control group, n=100) for 3 days post-gastroscopic mucosal biopsy. The presence of abdominal pain was observed pre-and post-gastroscopy, and the therapeutic effect of esomeprazole was assessed. This study was registered at the Chinese clinical trial registry as ChiCTR-TRC-00000500. RESULTS: Ten subjects were lost to followup (4 in treatment group; 6 in the control group). There was no significant difference in the number of subjects with aggravating abdominal pain (treatment 29.2% vs. control 22.3%; p>0.05) between the two groups. Esomeprazole did not significantly (p>0.05) affect the rate of abdominal pain within 24 h (treatment 27.1% vs. control 19.1%), 48 h (treatment 40.6% vs. control 27.7%), and 96 h (treatment 43.8% vs. control 34.0%) on abdominal pain in all in the evaluated subjects. Between the two groups however, a statistically significant difference (p<0.05) was found on overall effective treatment rates at 48 h (treatment 92.9% vs. control 66.7%) and at 96 h (treatment 100% vs. control 81%) in the subjects with worsened abdominal pain. CONCLUSIONS: The study suggests that routine prophylaxis with acid inhibitors is not recommended for all patients post-gastroscopic mucosal biopsy, however acid inhibitors should be administered for patients with aggravating abdominal pain.

Influence of endoscopic submucosal dissection on esophageal motility.

AIM: To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD). METHODS: Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed. RESULTS: Of the 12 patients enrolled, 1 patient had grade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia. CONCLUSION: Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.

Effect of HCV infection on expression of several cancer-associated gene products in HCC.

AIM:To study hepatocarcinogenesis of hepatitis C virus (HCV).METHODS: Expression of HCV antigens (CP10, NS3 and NS5) and several cancer-associated gene products (ras p21, c-myc, c-erbB-2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n = 46) and its surrounding liver tissue were studied by the ABC(avidin-biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group.RESULTS:Positive immunostaining with one, two or three HCV antigens was found in 20 (43.5%) cases,with either of two or three HCV antigens in 16 (34.8%) cases, and with three HCV antigens in 9 (19.6%) cases.Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20)was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups.CONCLUSION:HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibi ting the function of p16 gene, which acts as a negative regulator of cell cycle.