New therapy for renal cell carcinoma with down regulation of glycosyltransferase gene

我们研究了肾细胞癌(ROC)中甘露糖苷的变化与恶性潜能的关系，发现在转移过程中长链神经节苷脂增加，其中之一是二唾液酸糖基球戊糖神经酰胺(DSGb5)。本项目的目的是阐明DSGb5的功能作用。我们已经鉴定了2，6-唾液酸基转移酶(ST6GalNAcVI)催化唾液酸转移到单唾液糖基球状戊糖神经酰胺(MSGb5)以合成DSGb5。SiRNA下调ST6GalNAcVI基因的表达，导致体外培养的人肾癌细胞(ACHN细胞)活力下降，裸鼠ACHN细胞生长受阻。这些结果表明，DSGb5与ACHN细胞的运动和生长有关，下调ST6GalNac VI基因可能成为治疗肾癌的新方法。

We have investigated changes of ganliosides in renal cell carcinoma (ROC) in regard to the malignant potential and found that the long chain gangliosides increased in metastasis, one of which is disialosyl globopentaosylceramide (DSGb5). The purpose of this project is to clarify the functional role of DSGb5. We have identified that 2,6-sialyltransferase (ST6GalNAcVI) catalyzes transfer of sialic acid to monosialosyl globopentaosylceramide (MSGb5) to synthesizes DSGb5. Down-regulation of ST6GalNAcVI mRNA by siRNA has led to decreases of motility of human renal cell carcinoma cells (ACHN cells) in vitro and decreases of cell growth of ACHN in nude mice. From these findings, DSGb5 has relevance to motility and growth of ACHN cells and down-regulation of ST6GalNac VI gene may become a new therapy for RCC.