RESUMEN
The peritoneal implant metastasis is one of the main pathway and main cause for high mortality for gastric cancer metastasis. Researchs show that epithelial-mesenchymal transition (EMT) playing essential role in modulating gastric cancer metastasis, and the expression of hypoxia inducible factor-1α (HIF-1α) can promote EMT in tumor cells. This research aims to explore the influence and mechanism of Dextran Sulfate (DS) affecting EMT of human gastric cancer. In the present study, we found that DS can enter into the cytoplasm and function in it. Inhibition of HIF-1α or DS significantly inhibit the migration and invasion of human gastric cancer cells, and decrease the mRNA and protein expressions of HIF-1α, matrix metalloproteinase-2 (MMP-2), transforming growth factor-ß (TGF-ß), Twist and N-cadherin (N-cad), rise E-cadherin (E-cad) expression, DS with HIF-1α knockdown has a stronger effect. In vivo studies indicated that compared with using DS or HIF-1α knockdown alone, DS with HIF-1α knockdown can better suppress the volume and number of metastatic tumors, and reduce the mRNA and protein expressions of HIF-1α, MMP-2, TGF-ß, Twist and N-cad in metastatic tumor tissues of nude mice. We further demonstrated that the expression of HIF-1α, MMP-2, TGF-ß , Twist and N-cad were higher in well and poorly differentiated gastric cancer than paracancerous tissue, and poorly differentiated gastric cancer were even higher, while E-cad expression was opposite. Taken together, this study shows that DS can interfere the expression of HIF-1α, thereby inhibiting TGF-ß-mediated EMT of gastric cancer cells, and demonstrated a promising application of DS in gastric cancer therapy.
RESUMEN
BACKGROUND AND OBJECTIVE: Sapylin is one of the biological response modifiers. It has been used in the comprehensive treatment for advanced cancer, and its clinical efficacy has been proved. This study was to evaluate the effect of preoperative intraperitoneal injection of Sapylin in treatment of advanced gastric cancer. METHODS: Seventy-nine patients eligible for radical gastrectomy were randomly divided into the treatment group (Sapylin + mitomycin C, 40 patients) and the control group (mitomycin C alone, 39 patients). In the treatment group, 5 KE Sapylin was injected intraperitoneally 48 h before operation and 4 mg of mitomycin C was injected into peritoneal cavity before the closure of the peritoneum. In the control group, only 4 mg mitomycin C was injected into peritoneal cavity before the closure of the peritonium. RESULTS: There was no operative mortality or duodenal stump leakage in the two groups. Postoperative complications were anastomotic leakage (2.5%, 1/40) and incision rupture (2.5%, 1/40) in the treatment group, and incision rupture (2.6%, 1/39) in the control group, with no significant difference between the two groups (P > 0.05). The 3-year survival rate was significantly higher in the treatment group than in the control group (76.5% vs. 49.4%, P < 0.05). CONCLUSIONS: Preoperative intraperitoneal injection of Sapylin can raise the 3-year survival rate after radical gastrectomy , without increasing the incidence rate of operative complications. Preoperative intraperitoneal injection of Sapylin is therefore a valuable therapy for advanced gastric cancer in clinic.