1. Effects of triptolide on the sphingosine kinase - Sphingosine-1-phosphate signaling pathway in colitis-associated colon cancer.
- Author
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Li H, Xing X, Zhang X, Li L, Jiang Z, Wang T, Huang X, Wang X, Zhang L, and Sun L
- Subjects
- Animals, Azoxymethane, Colitis chemically induced, Colitis complications, Colitis pathology, Colitis-Associated Neoplasms etiology, Colitis-Associated Neoplasms pathology, Colon pathology, Dextran Sulfate, Disease Models, Animal, Epoxy Compounds pharmacology, Female, Humans, Male, Mice, Inbred BALB C, Mice, Inbred ICR, Mice, Nude, Signal Transduction drug effects, Sphingosine immunology, THP-1 Cells, Tumor-Associated Macrophages drug effects, Tumor-Associated Macrophages immunology, Colitis immunology, Colitis-Associated Neoplasms immunology, Diterpenes pharmacology, Lysophospholipids immunology, Phenanthrenes pharmacology, Phosphotransferases (Alcohol Group Acceptor) immunology, Sphingosine analogs & derivatives
- Abstract
Backgrounds: Triptolide (TP) exhibits effective activity against colon cancer in multiple preclinical models, but the mechanisms underlying the observed effects are not fully understood. Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in the regulation of colon cancer progression. The aim of this study was to investigate the effect of TP on the sphingosine kinase (SPHK)-S1P signaling pathway in colitis-associated colon cancer., Methods: An azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model and the THP-1 cell line were used to evaluate the therapeutic effects and mechanisms of TP in colitis-associated colon cancer (CACC). Various molecular cell biology experiments, including Western blotting, real-time PCR and immunofluorescence, were used to obtain relevant experimental data. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was also established to detect the levels of S1P in tissue and plasma., Results: In the AOM/DSS mouse model, TP treatment induced a dose-dependent decrease in tumor incidence and inhibited macrophage recruitment and M2 polarization in the tumors. TP also efficiently decreased the S1P levels and SPHK1/S1PR1/S1PR2 expression and significantly inhibited activation of the S1P-mediated phosphorylation of ERK protein in macrophages., Conclusions: The results indicated that TP might influence the recruitment and polarization of tumor-associated macrophages by suppressing the SPHK-S1P signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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