title: JSI-124 (Cucurbitacin I) inhibits tumor angiogenesis of human breast cancer through reduction of STAT3 phosphorylation.
abstract: Breast cancer (BC) is the most frequently diagnosed type of cancer all over the world. Angiogenesis, a physiological or pathological process characterized by the sprouting of new blood vessels from existing vessels, plays a vital role in tumor nutrition. In this work, we used JSI-124 (Cucurbitacin I), a selective JAK/STAT3 signaling pathway inhibitor, to investigate the role of STAT3 in tumor angiogenesis of a human BC cell line in vitro. JSI-124 inhibited cell viability, proliferation, adhesion, migration and tube formation of a human BC cell line MDA-MB-468. After transfection with pMXs-Stat3C, a dominant active mutant, the inhibitory effects of JSI-124 on MDA-MB-468 were abolished. Furthermore, JSI-124 reduced the phosphorylation of STAT3. These results suggested that JSI-124 inhibited tumor angiogenesis of the human BC cell line in vitro through the reduction of STAT3 phosphorylation. In addition, JSI-124 could reduce VEGF transcription and secretion, suggesting that JSI-124 is also involved in the inhibition of the VEGF autocrine loop in the tumor microenvironment.
authors: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, P. R. China.
authors: Jia
authors: J
authors: Qi
authors: Ge
authors: G
authors: Xia
authors: Cheng Rong
authors: CR
authors: Huang
authors: Jian Xia
authors: JX
authors: Wang
authors: Jian
authors: J
authors: Zhang
mesh_terms: D019898:Autocrine Communication / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; C038106:cucurbitacin I
keywords: Angiogenesis; Breast Cancer; JSI-124; STAT3 Inhibitor