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Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma
- Source :
- Cancer Letters. 432:144-155
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell cycle checkpoint
Angiogenesis
Angiogenesis Inhibitors
Apoptosis
Benzylisoquinolines
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Ovarian carcinoma
Autophagy
Tumor Cells, Cultured
Animals
Humans
PI3K/AKT/mTOR pathway
Cell Proliferation
Ovarian Neoplasms
Neovascularization, Pathologic
Chemistry
Macrophages
Cell Cycle
Cell cycle
Xenograft Model Antitumor Assays
Cystadenocarcinoma, Serous
Serous fluid
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Female
Human umbilical vein endothelial cell
Neoplasm Grading
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 432
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....1620e4296f10962fe279c02c52a65bda