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

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• 作者：Dongdong Han^a ; Chengjie Cao^a ; Ya Su^a ; Jun Wang^a ; Jian Sun^b ; Huasheng Chen^b ; Aihua Xu^a ; ^c ; ^{ahxu@yzu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cyclophosphamide (PubChem CID ; 2907) ; Mannose (PubChem CID ; 18950) ; Rhamnose (PubChem CID ; 25310) ; Galacturonic acid (PubChem CID ; 439215) ; Glucose (PubChem CID ; 5793) ; Galactose (PubChem CID ; 6036) ; Arabinose (PubChem CID ; 66308) ; Cis-Dichlorodiammine platinum(II) (PubChem CID ; 5702198)
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 November 2016
• 年：2016
• 卷：192
• 期：Complete
• 页码：406-412
• 全文大小：1709 K

文摘

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.

Aim of study

Study on the activity of GBEE against Lewis lung cancer (LLC) angiogenesis and its partial molecular mechanism.

Materials and methods

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, 200 mg/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 0.1 mL/10 g (b.w.), positive group were intraperitoneal (i.p.) injection cyclophosphamide (CPA) at a dose of 20 mg/kg (b.w.) , the GBEE treatment groups were respectively i.g. GBEE 50, 100, and 200 mg/kg (b.w.), once a day for 20 d. 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.

Results

GBEE suppressed the growth of LLC cells in a dose-dependent way at the dose of 5, 10, 20, 40, 80 and 160 µg/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, 200 mg/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.

Conclusions

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.