Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.
Invest New Drugs. 2020 Oct;38(5):1316-1325. doi: 10.1007/s10637-020-00909-2. Epub 2020 Feb 14.
Sphingosine-1-phosphate (S1P) is an important sphingolipid metabolite that regulates a wide range of physiological and pathophysiological processes. Our previous studies show that S1P selectively induces cell apoptosis in human breast cancer luminal A subtype cell line MCF7. In addition, S1P exhibits synergistic effects with chemotherapy drugs against both MCF7 and luminal B subtype cell line MDA-MB-361 at concentration in the high nM to low μM range. In the current study, we evaluated the effect of S1P on proliferation, apoptosis and cytotoxicity towards a panel of nine triple-negative breast cancer with basal-like morphology (TNBC-BL) cell lines (HCC1599, HCC1937, HCC1143, MDA-MB-468, HCC38, HCC70, HCC1806, HCC1187 and DU4475) in the same concentration range. S1P exhibited mild to moderate effects (<20% increase comparted to control) towards the TNBC-BL cell lines except HCC38, HCC70 and HCC1806. Furthermore, it increased cell apoptosis by ~15-20% in all the cell lines compared to the control, and elicited moderate to strong cytotoxic effect towards all cell lines except MDA-MB-468 and HCC1806. However, no synergistic/additive effect was observed between S1P and chemotherapy drug docetaxel for any TNBC-BL cell line.
鞘氨醇-1-磷酸（S1P）是一种重要的鞘脂代谢物，调节广泛的生理和病理生理过程。我们之前的研究表明，S1P 选择性诱导人乳腺癌管腔 A 亚型细胞系 MCF7 中的细胞凋亡。此外，S1P 在高 nM 至低 μM 浓度范围内与化疗药物对 MCF7 和管腔 B 亚型细胞系 MDA-MB-361 表现出协同作用。在本研究中，我们评估了 S1P 对一组具有基底样形态的九种三阴性乳腺癌（TNBC-BL）细胞系（HCC1599、HCC1937、HCC1143、MDA-MB-468、HCC38、HCC70、HCC1806、HCC1187 和 DU4475）增殖、凋亡和细胞毒性的影响，浓度范围相同。S1P 对除 HCC38、HCC70 和 HCC1806 之外的 TNBC-BL 细胞系表现出温和至中度的作用（与对照相比增加<20%）。此外，与对照相比，它使所有细胞系中的细胞凋亡增加了约 15-20%，并对所有细胞系产生了中度至强烈的细胞毒性作用，除 MDA-MB-468 和 HCC1806 之外。然而，在任何 TNBC-BL 细胞系中，S1P 与化疗药物多西他赛之间均未观察到协同/相加作用。
