JSI-124 (Cucurbitacin I) Inhibits Tumor Angiogenesis of Human Breast Cancer Through Reduction of STAT3 Phosphorylation
JSI-124 (Cucurbitacin I) Inhibits Tumor Angiogenesis of Human Breast Cancer Through Reduction of STAT3 Phosphorylation
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DOI：
10.1142/s0192415x15500226
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发表时间：
2015-01-01
影响因子：
5.7
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Qi, Jia;Xia, Ge;Zhang, Jian
乳腺癌（BC）是世界上最常见的癌症类型。血管生成是一种生理或病理过程，其特征是新血管从现有血管发芽，在肿瘤营养中起着至关重要的作用。在这项工作中，我们使用JSI-124（葫芦素I），选择性JAK/STAT 3信号通路抑制剂，研究STAT 3在体外人BC细胞系肿瘤血管生成中的作用。JSI-124抑制人BC细胞系MDA-MB-468的细胞活力、增殖、粘附、迁移和管形成。转染显性活性突变体pMXs-Stat 3C后，JSI-124对MDA-MB-468的抑制作用被消除。此外，JSI-124还减少了STAT 3的磷酸化。这些结果表明，JSI-124通过减少STAT 3磷酸化来抑制体外人BC细胞系的肿瘤血管生成。此外，JSI-124可减少VEGF的转录和分泌，表明JSI-124还参与抑制肿瘤微环境中的VEGF自分泌环。
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.