The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis

Abstract

Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis.

Sulfated polysaccharide-protein complex sensitizes doxorubicin-induced apoptosis of breast cancer cells in vitro and in vivo

“…SPPC has been observed to exhibit negligible cytotoxicity against normal cells; however, it markedly inhibited the proliferation of SMMC-7721 cells and blocked the cells in the S phase in a previous study (15). In addition, SPPC was shown to inhibit human SMMC-7721 cell growth in a dose-dependent manner (20), and it induced A B C cell apoptosis, increased the protein expression levels of caspase-3 and the drug excretion capacity of cells, and reduced the mRNA and protein expression levels of IL-8 (16). The present study demonstrated that co-treatment with SPPC and Dox markedly potentiated the antitumor activity of DOX against MDA-MB-231 human breast cancer cells.…”

“…In a study on the regulatory effect of sulfated polysaccharides on macrophage-induced tumor cell apoptosis, it was demonstrated that sulfated polysaccharides produced by L. japonica were able to indirectly enhance the cytotoxic effect of macrophages on HepG2 cells (16). However, the majority of previous studies have focused on the ability of SPPC to promote tumor cell apoptosis and inhibit tumor cell proliferation and metastasis when used alone (20,21); few studies have addressed whether SPPC has a synergistic effect when used simultaneously with other chemotherapeutic agents, such as Dox, with a view to clinically alleviate their toxicities. Therefore, the present study aimed to investigate the effect of SPPC on Dox-induced apoptosis of the MDA-MB-231 breast cancer cell line in vitro and in vivo.…”

Zoopharmacology: A Way to Discover New Cancer Treatments

“…Also, from whole animal aqueous extracts of Gekko swinhonis Güenter was isolated the Gekko Sulfated Glycopeptide or Gepsine. Gepsine exhibited anti-proliferative activity in Bel-702 and HT-29 cell lines; besides, it showed anti-angiogenic effects in human lymphatic endothelial cells (hLECs) due to disruption in bFGF function, which is a growth factor responsible for angiogenesis [ 73 , 74 ]. Moreover, the enzymatic hydrolysates of the three-striped box turtle ( Cuora trifasciata ) inhibit HepG2 and MCF-7 cells [ 75 ].…”

Traditional Chinese Medicine Regulating Lymphangiogenesis: A Literature Review

“…Afterwards, more recent studies by Ding et al. shown that GSPP, an extract of the gecko, acquires the antitumor properties by decreasing the expression of bFGF-inhibiting the growth of lymphatic vessels in vitro and in vivo , which may further suppress lymphatic metastasis ( Ding et al., 2016 ).…”

“…expression of VEGF-C and bFGFGecko powder(Zhang et al, 2011) BALB/c tumor-bearing mice 1.2 g/kg Gavage administration Affecting the expression of VEGF-C and not specific GSPP(Ding et al, 2016micro-blood vessel density and micro-lymphatic vessel density, 2) Inhibiting the expressions of CD31, VEGFR3, and VEGF-CResveratrol(Liu et al, 2018) 1) M2 macrophage/Human LECs 2) LM8-bearing mice 1) 1,5,10, 25, 50 mM 2) 10, 25 mg/kg, twice daily 1) Inhibited the migration, invasion of VEGF-C-induced Human LECs.2) Regulatied the activation and differentiation of M2 macrophage 3) Reduced the area of LECs (Continued)…”