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1-磷酸鞘氨醇和鞘氨醇磷酸胆碱对前列腺癌细胞系细胞内钙离子及细胞死亡的影响

Effects of sphingosine-1-phosphate and sphingosylphosphorylcholine on intracellular Ca2+ and cell death in prostate cancer cell lines.

作者信息

Mulders A C M, Nau S, Li Y, Michel M C

机构信息

Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Auton Autacoid Pharmacol. 2007 Oct;27(4):173-9. doi: 10.1111/j.1474-8673.2007.00410.x.

Abstract

The sphingolipid metabolites sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) can be involved in cellular growth and apoptosis, by both receptor-dependent and -independent mechanisms. We investigated the role of S1P and SPC in intracellular Ca2+ elevation, cell proliferation and cell death in DU 145 and PC3 hormone-refractory prostate cancer cell lines. S1P and SPC increased intracellular Ca2+ levels, most likely in a receptor-independent manner. Surprisingly, both S1P and SPC did not stimulate but rather reduced cell growth through induction of apoptosis. Therefore, antagonists targeted against S1P, SPC and their receptors do not appear to be promising new approaches in the treatment of hormone-refractory prostate cancer.

摘要

鞘脂代谢产物鞘氨醇-1-磷酸(S1P)和鞘氨醇磷酰胆碱(SPC)可通过受体依赖性和非依赖性机制参与细胞生长和凋亡。我们研究了S1P和SPC在DU 145和PC3激素难治性前列腺癌细胞系的细胞内Ca2+升高、细胞增殖和细胞死亡中的作用。S1P和SPC增加细胞内Ca2+水平,很可能是以受体非依赖性方式。令人惊讶的是,S1P和SPC均未刺激细胞生长,而是通过诱导凋亡来降低细胞生长。因此,针对S1P、SPC及其受体的拮抗剂似乎并非治疗激素难治性前列腺癌的有前景的新方法。

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