Ginkgo biloba exocarp extracts inhibits angiogenesis and its effects on Wnt/β-catenin-VEGF signaling pathway in Lewis lung cancer

• Published in: Journal of ethnopharmacology Vol. 192; pp. 406 - 412
• Main Authors: Han, Dongdong, Cao, Chengjie, Su, Ya, Wang, Jun, Sun, Jian, Chen, Huasheng, Xu, Aihua
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 04.11.2016
• Subjects: Angiogenesis; Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Arabinose (PubChem CID: 66308); beta Catenin - metabolism; Carcinoma, Lewis Lung - blood supply; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - metabolism; Carcinoma, Lewis Lung - secondary; Cell Movement - drug effects; Cell Proliferation - drug effects; Cis-Dichlorodiammine platinum(II) (PubChem CID: 5702198); Cyclophosphamide (PubChem CID: 2907); Cyclophosphamide - pharmacology; Dose-Response Relationship, Drug; Galactose (PubChem CID: 6036); Galacturonic acid (PubChem CID: 439215); Ginkgo biloba - chemistry; Ginkgo biloba exocarp extracts; Glucose (PubChem CID: 5793); Lewis lung cancer cells; Mannose (PubChem CID: 18950); Mice, Inbred C57BL; Microvessels - drug effects; Microvessels - metabolism; Microvessels - pathology; Neovascularization, Pathologic; Phosphorylation; Phytotherapy; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plants, Medicinal; Proto-Oncogene Proteins c-akt - metabolism; Rhamnose (PubChem CID: 25310); RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Burden - drug effects; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGF; VEGFR2; Wnt Signaling Pathway - drug effects; Wnt3a; Wnt3A Protein - metabolism; β-catenin; VEGFR2; Arabinose (PubChem CID: 66308); Glucose (PubChem CID: 5793); Cyclophosphamide (PubChem CID: 2907); Galacturonic acid (PubChem CID: 439215); VEGF; Lewis lung cancer cells; Ginkgo biloba exocarp extracts; Cis-Dichlorodiammine platinum(II) (PubChem CID: 5702198); β-catenin; Angiogenesis; Galactose (PubChem CID: 6036); Rhamnose (PubChem CID: 25310); Wnt3a; Mannose (PubChem CID: 18950)
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2016.09.018

A fruit of Ginkgo biloba L. also known as Ginkgo biloba, can be used for the treatment of cancer in Chinese traditional medicine. The scientific name of succulent skin, which is the episperm of Ginkgo nuts, is exocarp. Experiment shows that Ginkgo biloba exocarp extracts (GBEE) has the effects of immune promotion, cancer inhibition and etc. Study on the activity of GBEE against Lewis lung cancer (LLC) angiogenesis and its partial molecular mechanism. The effect of GBEE on proliferation of LLC cells was detected by MTT method in vitro. The metastasis model of LLC was set up. The C57BL/6J mice were randomly separated into normal control, model control, positive control and GBEE (50, 100, 200mg/kg) treatment groups, n=10. The mice in normal group and model group were both intragastric gavage (i.g.) normal saline (NS) in a volume of 0.1mL/10g (b.w.), positive group were intraperitoneal (i.p.) injection cyclophosphamide (CPA) at a dose of 20mg/kg (b.w.) , the GBEE treatment groups were respectively i.g. GBEE 50, 100, and 200mg/kg (b.w.), once a day for 20d. After treatment, we calculated the tumor inhibition rate and anti-metastasis rate. The microvessel density (MVD) was measured by immunohistochemistry method in transplanted tumor. The expression levels of vascular en-dothelial growth factor (VEGF) and VEGFR2 mRNA or Wnt3a, β-catenin, VEGF, VEGFR2 and p-Akt/Akt protein expression were respectively tested by Quantitative Reverse transcription Polymerase chain reaction (qRT-PCR) or western blot in vitro and vivo. GBEE suppressed the growth of LLC cells in a dose-dependent way at the dose of 5, 10, 20, 40, 80 and 160µg/mL in vitro. It can suppressed Wnt3a and β-catenin protein expression and the content of mRNA of VEGF and VEGFR2 in LLC cells significantly. In vivo, we discovered GBEE can retard the growth of LLC transplanted tumor in a dose-dependent way at the dose of 50, 100, 200mg/kg, suppressing tumor lung metastasis. The expression of CD34 was reduced, which means MVD was inhibited and so do β-catenin, VEGF, VEGFR2 and p-AKT/AKT protein expression and VEGF and VEGFR2 mRNA expression levels in LLC transplanted tumor of C57BL/6 mice. GBEE played the effects of anti-tumor and anti-metastatic depending upon the inhibition of tumor angiogenesis, which may be closely relevant to its effect in blockage of Wnt /β-catenin-VEGF signaling pathway in LLC. [Display omitted]