Study About Inhibition Of Cross-Linked Hyaluronic Acid Gel On Metastasis And Growth Of Gastric Cancer And Hepatic Cancer Cells

ObjectiveTo elucitrate the effect and mechanism of CHAG on migration, invasion, growth activities of gastric cancer and hepatic cancer cells in vitro.To elucitrate the effect of CHAG on colonization, growth and metastasis of gastric cancer and hepatic cancer cells in vivo and to definite whether the CHAG can be used in prevention of adhesion after abdominal tumorectomy. MethodsGastric cancer cell line AGS and hepatic cancer cell line Hep G2 were used as the research objects. Transwell assay and MTT assay were applied to study the effects of CHAG on migration, invasion and proliferation activities of the cells in vitro. The model of peritoneal transplantation tumor in nude mice was performed to observe the effect of CHAG on colonization, growth and metastasis of the cancer cells. Western Blotting, pull down assay and si RNA interference technology were applied to explore the mechanism of the effect of CHAG on the above biological activities of cancer cells. ResultsThe Transwell assay results showed that CHAG inhibited migration and invasion activities of gastric cancer and hepatic cancer cells induced by EGF. The MTT assay results showed that CHAG inhibited proliferation activities of gastric cancer and hepatic cancer cells induced by EGF. The results of experiment with the model of peritoneal transplantation tumor in nude mice showed that CHAG suppressed the colonization and growth of the cancer cells in peritoneal cavity. The results of Pull-down assay showed that CHAG inhibited LPA-induced activation of Rho A and EGF-induced activation of Rac1. The results of Western Blotting showed that CHAG blocked EGF-induced activation of EGFR, inhibited EGF/EGFR-stimulated signal transduction of MAPK/ERK and PI3K/Akt mediated pathways, and decreased EGF-induced expression of MMP2 and PCNA. Furthermore, CHAG had the inhibitory effect on activation of other membrane receptors, including integrin and VEGFR. The results of si RNA interference experiments showed that when the expression of HA receptors(CD44 and RHAMM) was interfered by si RNA, the above inhibitory effects of CHAG still existed, indicating that CHAG did not actualize its inhibition through binding with HA receptors but through physically covering the surface of the cells and thereby blocking the interaction between growth factors and their receptors. ConclusionCHAG can inhibit the growth and metastasis of gastric cancer and hepatic cancer cells. This inhibition was due to that CHAG physically covered cell surface, and blocked the binding between membrane receptors and their extracellular ligands.