Inhibition of Ovarian Cancer Chemoresistance and Metastasis with Antagonists of Hyaluronan-CD44-CD147 Interactions.

摘要

The overall objective of our work on human ovarian carcinoma cells is to apply our findings on the role of hyaluronan-CD44-CD147 interactions in drug resistance to improvement of therapy for malignant ovarian carcinoma. In previous work we showed that small hyaluronan oligosaccharides sensitize drug- resistant human ovarian carcinoma cells to various chemotherapeutic agents in culture and in vivo. In this grant period, we have: (a) shown that drug- resistant Hey-A8-MDR human ovarian carcinoma cells contain CD133-positive/ CD147-positive/ CD44-positive cancer stem-like cells, as are also found in human patient ascites-derived ovarian carcinoma cells, thus documenting their suitability for our studies; (b) completed preparation of hyaluronan oligosaccharide conjugated to the chemotherapeutic agent, docetaxel; we anticipate that this conjugate will show increased efficacy in vivo; (c) identified a highly active siRNA against the regulator of hyaluronan synthesis, CD147, that sensitizes Hey-A8-MDR ovarian carcinoma cells to docetaxel and is currently being used to load nanoparticles for higher efficacy in vivo.