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水飞蓟宾通过激活YAP的自噬降解来抑制前列腺癌的迁移、侵袭和上皮-间质转化。

Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP.

作者信息

Dan Weichao, Fan Yizeng, Hou Tao, Wei Yi, Liu Bo, Que Taotao, Yu Bixin, Zeng Jin, Li Lei

机构信息

Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

J Cancer. 2022 Sep 25;13(13):3415-3426. doi: 10.7150/jca.63514. eCollection 2022.

Abstract

Silibinin (SB), a flavonoid extracted from milk thistle seeds, has been found to exert antitumor effects in numerous tumor types. Our previous study reported that SB had anti-metastatic effects in prostate cancer (PCa). However, the exact underlying molecular mechanisms remain to be determined. The present study aimed to investigate the effects of SB on the migration, invasion and epithelial-mesenchymal transition (EMT) of castration-resistant PCa (CRPC) cells using wound healing, Transwell assays, and western blotting. The results revealed that SB treatment significantly inhibited the migration and invasion of CRPC cell lines. Moreover, SB was confirmed to activate autophagy, as determined using LC3 conversion, LC3 turnover and LC3 puncta assays. Further mechanistic studies indicated that the expression levels of Yes-associated protein (YAP) were downregulated in an autophagy-dependent manner after SB treatment. In addition, the SB-induced autophagic degradation of YAP was associated with the anti-metastatic effects of SB in CRPC. In conclusion, the findings of the present study suggested that SB might inhibit the migration, invasion and EMT of PCa cells by regulating the autophagic degradation of YAP, thus representing a potential novel treatment strategy for metastatic CRPC.

摘要

水飞蓟宾(SB)是一种从水飞蓟种子中提取的黄酮类化合物,已发现其在多种肿瘤类型中发挥抗肿瘤作用。我们之前的研究报道,SB对前列腺癌(PCa)具有抗转移作用。然而,确切的潜在分子机制仍有待确定。本研究旨在通过伤口愈合实验、Transwell实验和蛋白质免疫印迹法,研究SB对去势抵抗性前列腺癌(CRPC)细胞迁移、侵袭和上皮-间质转化(EMT)的影响。结果显示,SB处理显著抑制了CRPC细胞系的迁移和侵袭。此外,通过LC3转化、LC3周转和LC3斑点实验确定,SB可激活自噬。进一步的机制研究表明,SB处理后,Yes相关蛋白(YAP)的表达水平以自噬依赖的方式下调。此外,SB诱导的YAP自噬降解与SB对CRPC的抗转移作用相关。总之,本研究结果表明,SB可能通过调节YAP的自噬降解来抑制PCa细胞的迁移、侵袭和EMT,从而为转移性CRPC提供一种潜在的新型治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a3/9608209/40b39815190c/jcav13p3415g001.jpg

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