Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, P. R. China.
Am J Chin Med. 2015;43(2):337-47. doi: 10.1142/S0192415X15500226. Epub 2015 Mar 19.
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.
乳腺癌（BC）是全世界最常见的癌症类型。血管生成，一种以新血管从现有血管中发芽为特征的生理或病理过程，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），一种选择性 JAK/STAT3 信号通路抑制剂，来研究 STAT3 在体外人乳腺癌细胞系肿瘤血管生成中的作用。JSI-124 抑制了人乳腺癌细胞系 MDA-MB-468 的细胞活力、增殖、黏附、迁移和管状形成。用 pMXs-Stat3C 转染后，一种显性激活突变体，JSI-124 对 MDA-MB-468 的抑制作用被消除。此外，JSI-124 降低了 STAT3 的磷酸化。这些结果表明，JSI-124 通过降低 STAT3 的磷酸化来抑制体外人乳腺癌细胞系的肿瘤血管生成。此外，JSI-124 可以减少 VEGF 的转录和分泌，表明 JSI-124 还参与了肿瘤微环境中 VEGF 自分泌环的抑制。
