Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Invest New Drugs. 2011 Apr;29(2):396-9. doi: 10.1007/s10637-009-9375-9. Epub 2009 Dec 30.
Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and progression. Its cellular concentration is controlled predominantly by sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current study we showed that mRNA expressions for both SK and SPL were up-regulated throughout all four disease stages in human breast cancer patients. Exogenous administration of S1P produced a bell-shaped dose response for apoptosis in normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in breast cancer MCF7 cells. Co-administration of S1P enhanced the cytotoxicity of anticancer drug docetaxel against MCF7 cells.
鞘氨醇-1-磷酸（S1P）是癌症发展和进展的重要调节剂。其细胞浓度主要由鞘氨醇激酶（SK）和鞘氨醇-1-磷酸裂解酶（SPL）控制。在本研究中，我们表明，在人类乳腺癌患者的所有四个疾病阶段，SK 和 SPL 的 mRNA 表达均上调。外源性 S1P 给药对正常乳腺 MCF12A 细胞的凋亡呈钟形剂量反应，而对乳腺癌 MCF7 细胞的凋亡呈 S 形反应。S1P 的共同给药增强了抗癌药物多西他赛对 MCF7 细胞的细胞毒性。
