JSI-124 (Cucurbitacin I) inhibits tumor angiogenesis of human breast cancer through reduction of STAT3 phosphorylation

• Published in: The American journal of Chinese medicine (1979) Vol. 43; no. 2; p. 337
• Main Authors: Qi, Jia, Xia, Ge, Huang, Cheng Rong, Wang, Jian Xia, Zhang, Jian
• Format: Journal Article
• Language: English
• Published: Singapore 2015
• Subjects: Autocrine Communication - drug effects; Breast Neoplasms - blood supply; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Adhesion - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Cell Transformation, Neoplastic - drug effects; Depression, Chemical; Female; Humans; Molecular Targeted Therapy; Neovascularization, Pathologic - drug therapy; Phosphorylation - drug effects; Phytotherapy; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; STAT3 Transcription Factor - physiology; Transcription, Genetic - drug effects; Triterpenes - pharmacology; Triterpenes - therapeutic use; Tumor Microenvironment - drug effects; Tumor Microenvironment - genetics; Vascular Endothelial Growth Factor A - genetics; Angiogenesis; Breast Cancer; JSI-124; STAT3 Inhibitor
• ISSN: 0192-415X
• DOI: 10.1142/S0192415X15500226

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.