通过透明质酸CD44-CD147相互作用的拮抗剂抑制卵巢癌化疗耐药和转移
Inhibition of Ovarian Cancer Chemoresistance and Metastasis with Antagonists of Hyaluronan-CD44-CD147 Interactions
关键词:化疗药物;卵巢肿瘤细胞(生物学)
摘 要:The overall objectives of our work on human ovarian carcinoma cells are to determine the mechanisms whereby hyaluronan-CD44-CD147 interactions influence malignant cell behavior and therapy resistance, and to apply our findings to the improvement of therapy, in malignant ovarian carcinoma. In this grant period we have shown that small hyaluronan oligosaccharides, which have previously been shown to antagonize hyaluronan-receptor interactions, sensitize cisplatin-resistant human ovarian carcinoma cells to cisplatin treatment in a mouse xenograft model, as well as in cell culture. Hyaluronan oligosaccharide- decorated nanoparticles containing chemotherapeutic agents are in preparation for maximizing these effects. We have also shown that siRNAs against the hyaluronan receptor, CD44, and the regulator of hyaluronan synthesis, CD147, sensitize cisplatin-resistant ovarian carcinoma cells to cisplatin in cell culture. Nanoparticles containing these siRNAs are in preparation for use in vivo.