title: Arsenic trioxide exerts anti-lung cancer activity by inhibiting angiogenesis.
abstract: Arsenic trioxide (As2O3) has been used in the clinic for the treatment of acute promyelocytic 1eukemia and some solid tumors. However, its effectiveness against lung cancer has not been well demonstrated, and the underlying mechanism(s) of action remain unclear. In the present study, we found that As2O3 significantly inhibited the growth of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) xenograft tumors. It was observed to have antiangiogenic effects in xenograft models and matrigel pellets. It also significantly inhibited the expression of VEGF-A, VEGFR-2, HIF-1α, Dll4 and Notch-1 in vivo. Moreover, As2O3 also inhibited the expression of HIF-1α, VEGFR-2, Dll4, and Notch-1 in lung cancer cell lines and human umbilical vein endothelial cells. These findings suggest that As2O3 has significant anti-lung cancer activity, which may occur as a result of the antiangiogenic effects caused by the downregulation of the VEGF and Dll4-Notch signaling pathways.
authors.forename: Meng-Hang
authors.initials: MH
authors.lastname: Yang
authors.forename: Yuan-Sheng
authors.initials: YS
authors.lastname: Zang
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. xuewei-zhao@hotmail.com.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002135:Calcium-Binding Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D010087:Oxides / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / 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
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors; D001152:Arsenicals; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; C497761:NOTCH1 protein, human; D010087:Oxides; D051881:Receptor, Notch1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077237:Arsenic Trioxide