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Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved.Methods: After treating Human umbilical vein endothelial cells (HUVEC) and HepG2 cells with different concentrations of triptolide (TP), the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids.Results: This study explored the effects of TP on the proliferation, migration, adhesion and tube formation of HUVEC cells, as well as the effects on the proliferation, migration and invasion of HepG2 cells. And through the PCR Array assay to screen the changes of related sphingolipid genes, it was found that serine palmitoyltransferase long chain base subunit 2 (SPTLC2) was most likely to be related to the effect of TP. In further transfection experiments, it was found that down-regulation of SPTLC2 can inhibit the proliferation, migration, adhesion and tube formation of HUVEC cells, and down-regulation of SPTLC2 can also inhibit the proliferation, migration and invasion of HepG2 cells. The up-regulation of SPTLC2 has opposite effects in these two cell lines. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC cells can promote the biological process of HepG2 cells. It was found through enzyme linked immunosorbent assay (ELISA) and western blot experiments that it may be achieved through the sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) pathway. Finally, we found that the promotion effect of HUVEC cells on HepG2 cells was significantly inhibited after HUVEC cells were treated with TP.Conclusions: These data confirmed that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there was a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets. |
