Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

Abstract

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1a (HIF-1a), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1a and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-a was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

Fucoxanthin Exerts Anti-Tumor Activity on Canine Mammary Tumor Cells via Tumor Cell Apoptosis Induction and Angiogenesis Inhibition

“…Furthermore, it also reduces the protein expression of Bcl-2, an anti-apoptotic protein, in prostate cancer and human promyelocytic leukemia [ 11 , 14 , 15 ]. Moreover, the anti-angiogenic activity of several natural products has been reported in various cancer cells [ 16 , 17 , 18 ]. However, no evidence exists regarding the anti-tumor potential of fucoxanthin in canine mammary gland tumors.…”

Based on the Effect of Huazhengsanji Prescription and Cisplatin on Hypoxia-Induced HepG2 Hepatoma Cells HIF-1α and VEGF

“…It regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis [15] . Studies have shown that [16] hypoxia can promote HIF-1α mRNA and protein levels in Hepatoma cells. This experiment found that the expression of HIF-1α protein in the model group was signi cantly higher than that in the control group.…”

miR-3156-5p Enhances Hypoxia-Induced Angiogenesis in Hepatocellular Carcinoma via Modulating the SOCS5/HIF-1α/VEGF Pathway

“…Human umbilical vein endothelial cells (HUVECs) were purchased from Allcells (Shanghai, China) and cultured in the medium containing 50 U/mL penicillin and 50 U/mL streptomycin (Invitgen, San Diego, CA), 50 mL endothelial cell growth additive (Upstate, Temecula, CA), 2.2 g/L sodium bicarbonate, and 10% fetal bovine serum (Gibco, Grand Island, NY) under a humid environment at 37˚C with 5% CO 2 [19].…”

“…Liu K et al showed that HIF-1α and VEGF expression in the serum of HCC patients was elevated after TACE [17]. Besides, inhibiting the HIF-1α/VEGF pathway under hypoxia chokes HCC tumorigenicity and angiogenesis [18,19]. Thus, inhibiting the HIF-1α/VEGF pathway has guiding signi cance for the treatment of HCC.…”