Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis

被引:124
作者
Lin, Jiumao [1 ,2 ]
Wei, Lihui [1 ,2 ]
Shen, Aling [1 ]
Cai, Qiaoyan [1 ,2 ]
Xu, Wei [3 ]
Li, Huang [3 ]
Zhan, Youzhi [1 ,2 ]
Hong, Zhenfeng [1 ]
Peng, Jun [1 ,2 ]
机构
[1] Fujian Univ Tradit Chinese Med, Acad Integrat Med Biomed Res Ctr, Fuzhou 350122, Fujian, Peoples R China
[2] Fujian Univ Tradit Chinese Med, Fujian Key Lab Integrat Med Geriatr, Fuzhou 350122, Fujian, Peoples R China
[3] Fujian Univ Tradit Chinese Med, Dept Pharmacol, Fuzhou 350122, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
Hedyotis diffusa Willd; Chinese medicine; colorectal cancer; angiogenesis; sonic hedgehog signal pathway; ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; NATURAL-PRODUCTS; COLON-CANCER; MOUSE MODEL; PATHWAY; MECHANISMS; METASTASIS; VEGF;
D O I
10.3892/ijo.2012.1753
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Sonic hedgehog (SHH) signaling pathway promotes the process of angiogenesis, contributing to the growth and progression of many human malignancies including colorectal cancer (CRC), which therefore has become a promising target for cancer chemotherapy. Hedyotis diffusa Willd (HDW), as a well-known traditional Chinese herbal medicine, has long been used in China for the clinic treatment of various cancers. Recently, we reported that HDW can inhibit colorectal cancer growth in vivo and in vitro via suppression of the STAT3 pathway. In addition, we demonstrated the anti-angiogenic activity of HDW in vitro. To further elucidate the mechanism of the tumoricidal activity of HDW, by using a CRC mouse xenograft model we evaluated the in vivo effect of the ethanol extract of HDW (EEHDW) on tumor angiogenesis, and investigated the underlying molecular mechanisms. We found that EEHDW could significantly reduce intratumoral microvessel density (MVD), indicating its activity of antitumor angiogenesis in vivo. EEHDW suppressed the activation of SHH signaling in CRC xenograft tumors since it significantly decreased the expression of key mediators of SHH pathway. EEHDW treatment inhibited the expression of the critical SHH signaling target gene VEGF-A as well as its specific receptor VEGFR2. Taken together, we propose for the first time that Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of SHH-mediated tumor angiogenesis.
引用
收藏
页码:651 / 656
页数:6
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