Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma. (28th September 2018)

• Record Type: Journal Article
• Authors: Zhang, Qing; Li, Yinuo; Miao, Chunying; Wang, Yuqiong; Xu, Ying; Dong, Ruifen; Zhang, Zhiwei; Griffin, Brannan B.; Yuan, Cunzhong; Yan, Shi; Yang, Xingsheng; Liu, Zhaojian; Kong, Beihua
• Is Part Of: Cancer letters. Volume 432(2018)
• Page Start: 144
• Page End: 155
• Publication Date: 2018-09-28
• Subjects: Anti-angiogenesis -- Neferine -- Autophagy -- TAMs -- HGSOC; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.05.049
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecologic malignancies. Currently, anti-angiogenesis therapy is the most promising strategy for the successful treatment of HGSOC. In this study, we found Neferine could inhibit the angiogenesis of ovarian cancer cells both in vitro and in vivo . Further analysis revealed that its suppressive effect on human umbilical vein endothelial cell (HUVEC) proliferation correlated with promoting cell cycle arrest and autophagy. The cell cycle genes were dose-dependently reduced and the level of LC3II/LC3I (microtubule associated protein 1 light chain 3) was increased. Using a specific marker for macrophages (CD206 and Mrc1), we indicated that Neferine could inhibit M2-macrophage in vivo . Finally, CD206 was stained in 150 HGSOC samples and its high expression predicted inferior overall survival. Our current study is the first to demonstrate the anti-angiogenesis mechanism of Neferine by inducing autophagy via mTOR/p70S6K pathway inhibition and suppressing M2-macrophage polarization. Our findings suggest that Neferine is an attractive reagent with great potential in HGSOC therapy, especially in standard-therapy resistant cases. Highlights: Neferine can inhibit the angiogenesis of HGSOC both in vitro and in vivo . Neferine can promote autophagy via mTOR/p70S6K pathway inhibition. Neferine can inhibit M2-macropahage polarization. High expression of CD206 predicted significantly worse overall survival of HGSOC.