Cross-linked hyaluronan gel inhibits the growth and metastasis of ovarian carcinoma.

Background: The recurrence, metastasis and poor prognosis are important characteristics of ovarian carcinoma (OC), which are associated with exfoliation of cells from the primary tumor and colonization of the cells in pelvic cavity. On the other hand, the life quality of the patients undergoing surgical resection of OC was influenced by postoperative adhesions. Therefore, preventing postoperative implant tumor and adhesion may be effective methods to improve OC treatment. HyaRegen Gel, a cross-linked hyaluronan gel (CHAG), has been widely used as an anti-adhesive agent following pelvic operation in clinic. However, whether it can affect the implantation and growth of OC cells or not is still not clear.

Methods: Migration and invasion assays were applied to detect the effect of CHAG on migration and invasion of OC cells. Western blotting was performed to detect the phosphorylation/activation of EGFR and ERK, and the expression of PCNA and MMP7. Pull down assay was used to analyze the effect of CHAG on the activation of small G protein Rac1. Nude mice implantation tumor model was applied to observe the effect of CHAG on implantation tumor of OC cells.

Results: The results of in vitro experiments showed that CHAG suppressed both basic and EGF-induced migration and invasion of OC cells, blocked the activation of EGF-initiated EGFR activation, inhibited downstream signal transduction of EGFR, and decreased expression of proliferation and migration/invasion related proteins. Meanwhile, results of in vivo experiments showed that CHAG not only inhibited the formation of implantation tumor of OC cells but also delayed the of the growth of the tumors.

Conclusions: CHAG inhibited migration, invasion and proliferation of OC cells in vitro, and suppressed development of implantation tumor of OC in vivo. This made it as both anti-tumor and anti-adhesion agents.