Arsenic Trioxide Suppresses Tumor Growth through Antiangiogenesis via Notch Signaling Blockade in Small-Cell Lung Cancer.
Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As2O3) was reported to exert antiangiogenesis activities against lung cancer and induce poor development of vessel structures, similar to the effect observed fo...
| Publicado en: | BioMed Research International pp. 1 - 10 |
|---|---|
| Autores principales: | , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
4/10/2019
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135817969&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135817969 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 4/10/2019 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 135817969 135817969 135817969 10.1155/2019/4647252 135817969 ppf: 1 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Arsenic Trioxide Suppresses Tumor Growth through Antiangiogenesis via Notch Signaling Blockade in Small-Cell Lung Cancer. aug: au: Yang, Meng-Hang Chang, Ke-Jie Li, Bing Chen, Wan-Sheng affil: Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China sug: subj: Arsenicals Pharmacodynamics Cell Line, Tumor Drug Effects Signal Transduction Drug Effects Neovascularization, Physiologic Drug Effects Membrane Proteins Drug Effects Carcinoma, Non-Small-Cell Lung Drug Therapy Human Transcription Factors Drug Effects Blood Vessels Drug Effects In Vivo Studies Gene Expression Drug Effects Umbilical Veins Drug Effects Epithelial Cells Drug Effects ab: Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As2O3) was reported to exert antiangiogenesis activities against lung cancer and induce poor development of vessel structures, similar to the effect observed following the blockade of Notch signaling. However, there are no direct evidences on the inhibitory effects of As2O3 on tumor growth and angiogenesis via blockade of Notch signaling in SCLC. Here, we found that As2O3 significantly inhibited the tumor growth and angiogenesis in SCLC and reduced the microvessel density. As2O3 disturbed the morphological development of tumor vessels and downregulated the protein levels of delta-like canonical Notch ligand 4 (Dll4), Notch1, and Hes1 in vivo. DAPT, a Notch signaling inhibitor, exerted similar effects in SCLC. We found that both As2O3 treatment and Notch1 expression knockdown resulted in the interruption of tube formation by human umbilical vein endothelial cells (HUVECs) on Matrigel. As2O3 had no effects on Dll4 level in HUVECs but significantly inhibited the expression of Notch1 and its downstream gene Hes1 regardless of Dll4 overexpression or Notch1 knockdown. These findings suggest that the antitumor activity of As2O3 in SCLC was mediated via its antiangiogenic effect through the blockade of Notch signaling, probably owing to Notch1 targeting. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|