Sini Decoction containing serum modulates the expression of angiogenesis-associated molecules in HUVECs by regulating the signalling pathway VEGF-Dll4/Notch1 and p38MAPK/ERK1/2/p-AKT
Sini Decoction inhibits tumour angiogenesis
DOI:
https://doi.org/10.56042/ijeb.v62i12.6850Keywords:
Traditional Chinese Medicine, Medical oncology, Treatment, Vascular endothelial cellsAbstract
Angiogenesis is crucial for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) and Notch ligand Delta-like 4 (Dll4) play a critical role in vessel formation and angiogenesis. This study aimed to determine anti-angiogenesis effects of Sini Decoction serum on human umbilical vein endothelial cells (HUVECs). We prepared Sini Decoction serum in doses of 0.925, 1.85, 3.7 g/mL, and administered to HUVECs. HUVECs migration was evaluated using a wound healing assay. Formation of tube-like structures in HUVECs was observed using a tube-formation assay. Gene transcriptions of Dll4, Notch1, VEGF receptor 2 (VEGFR-2) and VEGF were examined using a PCR assay. Protein expressions of Janus kinase-2/signal transducer and activator of transcription 3 (JAK2/STAT3) molecules and signal molecules downstream of VEGF/VEGFR related to angiogenesis (including mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase-1/2 (ERK1/2), focal adhesion kinase (FAK) and phosphorylated protein kinase B (p-Akt)) were detected by western blot. Sini Decoction serum significantly inhibited cell migration and the formation of tube-shaped structures in HUVECs compared to Control group (P<0.05). Sini Decoction serum markedly decreased Dll4, Notch1, VEGF, and increased VEGFR-2 gene transcriptions, compared to those of Control group (P<0.05). Sini Decoction serum significantly reduced expression of p-Akt, p38MAPK and ERK1/2, compared to Control group (P<0.05). Although a reduction in FAK and STAT3 expression was discovered in HUVECs administered by Sini Decoction serum, without statistical significance compared to Control group (P>0.05). In conclusion, Sini Decoction serum modulated the expression of angiogenesis-associated molecules in HUVECs by activating VEGF-Dll4/Notch1 and p38MAPK/ERK1/2/p-AKT signalling pathways.