title: Salinomycin exhibits anti-angiogenic activity against human glioma in vitro and in vivo by suppressing the VEGF-VEGFR2-AKT/FAK signaling axis.
abstract: Tumor angiogenesis plays a crucial role in tumor growth, progression and metastasis, and suppression of tumor angiogenesis has been considered as a promising anticancer strategy. Salinomycin (SAL), an antibiotic, displays novel anticancer potential against several human cancer cells in vitro and in vivo. However, little information concerning its anti-angiogenic properties is available. Therefore, the anti‑angiogenic effect of SAL and the underlying mechanism in human glioma were evaluated in the present study. The results indicated that SAL treatment significantly inhibited human umbilical vein endothelial cell (HUVEC) proliferation, migration, invasion and capillary-like tube formation. Further investigation on intracellular mechanisms showed that SAL markedly suppressed FAK and AKT phosphorylation, and downregulated vascular endothelial growth factor (VEGF) expression in HUVECs. Pretreatment of cells with a PI3K inhibitor (LY294002) and FAK inhibitor (PF562271) markedly enhanced SAL-induced inhibition of HUVEC proliferation and migration, respectively. Moreover, U251 human glioma xenograft growth was also effectively blocked by SAL treatment in vivo via inhibition of angiogenesis involving FAK and AKT depho-sphorylation. Taken together, our findings validated that SAL inhibits angiogenesis and human glioma growth through suppression of the VEGF-VEGFR2-AKT/FAK signaling axis, indicating the potential application of SAL for the treatment of human glioma.
authors.affiliation: Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, P.R. China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Bi
authors.affiliation: Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, P.R. China.
authors.forename: Pei-Yan
authors.initials: PY
authors.lastname: Mi
authors.affiliation: Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong 271000, P.R. China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Heng-Ming
authors.initials: HM
authors.lastname: Pan
authors.affiliation: Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, P.R. China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Taian Central Hospital, Taian, Shandong 271000, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong 271000, P.R. China.
authors.forename: Lu-Rong
authors.initials: LR
authors.lastname: Shao
authors.affiliation: Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong 271000, P.R. China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, P.R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000095662:Polyether Polyketides
chemical_list: D020533:Angiogenesis Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011714:Pyrans; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C010327:salinomycin; D000095662:Polyether Polyketides