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棉酚通过逆转上皮间质转化和抑制蛋白酶活性抑制肺腺癌细胞转移。

Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity.

机构信息

Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

Environ Toxicol. 2024 Nov;39(11):5209-5221. doi: 10.1002/tox.24363. Epub 2024 Sep 12.

DOI:10.1002/tox.24363
PMID:39263880
Abstract

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.

摘要

棉酚,一种天然多酚化合物,具有抗病毒活性,并诱导多种类型肿瘤细胞死亡。然而,棉酚对肺癌转移和上皮间质转化的疗效尚不清楚。本工作旨在确定棉酚对人肺癌细胞的抗癌和抗转移作用的细胞和分子机制。棉酚对 H1299 和 A549 细胞的活力、迁移和侵袭有明显的抑制作用。明胶酶谱分析表明,棉酚足以抑制尿激酶型纤溶酶原激活物和基质金属蛋白酶-2 的活性。棉酚逆转了 TGF-β诱导的上皮间质转化。棉酚降低了波形蛋白、p-FAK、p-Src 和 p-paxillin。通过在免疫缺陷 BALB/c 裸鼠和严重联合免疫缺陷小鼠中皮下接种和尾静脉注射 A549 进行了棉酚的体内研究。

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