Ginkgo biloba exocarp extracts inhibits metastasis and its effects on TGF-β1/ERK1/2/MMP-9 signaling pathway in B16-F10 melanoma

作     者：LUO Cheng-rong WANG Meng-meng GAO Yan-qi CHEN Hua-sheng XU Ai-hua 

作者机构：Institute of Translational Medicine Medical CollegeYangzhou University 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2019年第10期

页      面：884-885页

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Medical High-tech Re-search Projects of Jiangsu Province(BG2007609) Science and Technology Innovation Fund Projects of College Students in Yangzhou University(x20180720) 

主　　题：GBEE metastasis B16-F10 TGF-β1/ERK1/2/MMP-9 

摘      要：OBJECTIVE To study the inhibition and mechanism of Ginkgo biloba exocarp extracts（GBEE）for the metastasis of B16-F10 melanoma in C57 BL/6 J mice. METHODS The metastasis model of B16-F10 in C57BL/6J mice was set up. The C57 BL/6 J mice were randomly separated into these groups: positive control,model control, normal control and GBEE treatment groups, n=10. The mice in positive group wereintraperitoneal（ip） injectioncis-dichlorodiamineplatinum（Ⅱ） at a dose of 5 mg·kg-1, twice a day for 7 d; model group and normal group were both intragastric gavage（ig） normal saline（NS） in a volume of 0.1 m L/10 g, once a day for17 d; the GBEE treatment groups were respectively ig GBEE 50, 100 and 200 mg · kg-1, once a day for 17 *** the administration, the lung tissue was removed and the lung surface metastasis was observed; the rate of lung metastasis and anti-metastasis were calculated;the degree of lung metastasis was observed by HE staining; in vitro, the effect of GBEE on the migration rate of B16-F10 cel s was detected by wound healing test; Western Blot was used to detect the expression of TGF-β1, ERK1/2,p-ERK1/2 and MMP-9 protein in B16-F10 cel s. RESULTS In vivo, we discovered that GBEE(50, 100, 200 mg·kg-1)cansuppress tumor lung metastasis of B16-F10 melanoma in C57 BL/6 J mice in a dose-dependent way. In vitro, we found that GBEE(20, 40, 80 mg·L-1) can significantly inhibit B16-F10 cells treated for 24 h and 48 h migration in a time-and concentration-dependent way. GBEE(20, 40,80 mg ·L-1) can suppressed TGF-β1, p-ERK1/2/ERK1/2 and MMP-9 protein expression level in a concentrationdependent way. CONCLUSION GBEE significantly inhibit the metastasis of B16-F10 melanoma, and its mechanism of action is related to the inhibition of extracellular matrix degradation and cell migration through the TGF-β1/ERK1/2/MMP-9 signaling pathway.