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Sphingomyelin potentiates chemotherapy of human cancer xenografts.

Abstract：

:We propose that one manifestation of altered sphingolipid metabolism within tumor cells may be a reduced sensitivity to anti-cancer therapies because of an inability to produce a sufficient apoptotic signal via sphingomyelin hydrolysis to ceramide. If so, then sphingomyelin administration could reverse this effect and increase a tumor's sensitivity to chemotherapy. In vivo, intravenous sphingomyelin (10 mg/day, 7 days) potentiated 5-fluorouracil chemotherapy (0.45 mg/day, 5 days) when co-administered to HT29 human colonic xenograft-bearing nude mice. In vitro, sphingomyelin (SM) at its maximum tolerated concentration increased 5-fluorouracil and doxorubicin sensitivity of HCT15 and MOSER (1 mg/ml SM) and LS174T and SW480 human colonic tumor cells (0.1 mg/ml) approximately 100-300%. At 1 mg/ml SM, however, no effect was seen using HT29, LoVo and WiDr cells. There was no sensitization of normal human umbilical cord endothelial cells. Thus, sphingomyelin co-administration may be one method to improve the selective efficacy of chemotherapy in some tumors, possibly through enhancement of the apoptotic response.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Modrak DE,Lew W,Goldenberg DM,Blumenthal R

doi

10.1006/bbrc.2000.2178

subject

Has Abstract

pub_date

2000-02-16 00:00:00

pages

603-6

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)92178-8

journal_volume

268

pub_type

杂志文章

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