Use of a Glycolipid Inhibitor to Ameliorate Renal Cancer in a Mouse Model

作者：Chatterjee Subroto^*; Alsaeedi Nezar; Hou Jennifer; Bandaru Veera Venkata Ratnam; Wu Lan; Halushka Marc K; Pili Roberto; Ndikuyeze Georges; Haughey Norman J

来源：PLos One, 2013, 8(5): e63726.

DOI：10.1371/journal.pone.0063726

In a xenograft model wherein, live renal cancer cells were implanted under the kidney capsule in mice, revealed a 30-fold increase in tumor volume over a period of 26 days and this was accompanied with a 32-fold increase in the level of lactosylceramide (LacCer). Mice fed D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of glucosylceramide synthase and lactosylceramide synthase (LCS: b-1,4-GalT-V), showed marked reduction in tumor volume. This was accompanied by a decrease in the mass of lactosylceramide and an increase in glucosylceramide (GlcCer) level. Mechanistic studies revealed that D-PDMP inhibited cell proliferation and angiogenesis by inhibiting p44MAPK, p-AKT-1 pathway and mammalian target for rapamycin (mTOR). By linking glycosphingolipid synthesis with tumor growth, renal cancer progression and regression can be evaluated. Thus inhibiting glycosphingolipid synthesis can be a bonafide target to prevent the progression of other types of cancer.

• 出版日期2013-5-9