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评估鞘氨醇-1-磷酸对具有基底样形态的人三阴性乳腺癌细胞的抗肿瘤活性。

Evaluating the antitumor activity of sphingosine-1-phosphate against human triple-negative breast cancer cells with basal-like morphology.

机构信息

Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.

出版信息

Invest New Drugs. 2020 Oct;38(5):1316-1325. doi: 10.1007/s10637-020-00909-2. Epub 2020 Feb 14.

Abstract

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.

摘要

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。

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