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甘草素通过激活内质网应激抑制前列腺癌细胞的迁移、侵袭和 EMT。

Liquiritigenin inhibits the migration, invasion, and EMT of prostate cancer through activating ER stress.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, PR China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China.

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, PR China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China.

出版信息

Arch Biochem Biophys. 2024 Nov;761:110184. doi: 10.1016/j.abb.2024.110184. Epub 2024 Oct 22.

DOI:10.1016/j.abb.2024.110184
PMID:39447623
Abstract

Liquiritigenin (LQ) is a monomeric compound found in licorice, a leguminous plant, and has been reported to exhibit antitumor effects in various lines of cancer cells. However, the underlying molecular mechanisms by which LQ exerts its antitumor effects remain largely unknown. In this study, the effects of LQ on the migration, invasion, and epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells were investigated. We found that LQ effectively inhibited the migration and invasion of PCa cells in vitro, and this effect was further confirmed in xenograft lung metastasis models. In addition, LQ was found to activate endoplasmic reticulum stress (ER stress) in PCa cells. Further studies found that LQ upregulated the expression of inositol-requiring enzyme type 1α (IRE1). When IRE1 was knocked down, we observed a weakened inhibitory effect of LQ treatment on the migration and invasion of PCa cells. This observation suggests that LQ may inhibit the migration, invasion and EMT of PCa cells through activating the IRE1 branch of ER stress. In conclusion, our research may provide a novel therapeutic strategy for PCa.

摘要

甘草素(LQ)是一种存在于甘草中的单体化合物,已被报道在多种癌细胞系中具有抗肿瘤作用。然而,LQ 发挥抗肿瘤作用的潜在分子机制在很大程度上尚不清楚。在这项研究中,研究了 LQ 对前列腺癌细胞(PCa)迁移、侵袭和上皮-间充质转化(EMT)的影响。我们发现 LQ 能有效抑制 PCa 细胞在体外的迁移和侵袭,这一作用在异种肺转移模型中得到了进一步证实。此外,发现 LQ 能激活 PCa 细胞中的内质网应激(ER 应激)。进一步的研究发现,LQ 上调了肌醇需求酶 1α(IRE1)的表达。当敲低 IRE1 时,我们观察到 LQ 处理对 PCa 细胞迁移和侵袭的抑制作用减弱。这一观察结果表明,LQ 可能通过激活 ER 应激的 IRE1 分支来抑制 PCa 细胞的迁移、侵袭和 EMT。总之,我们的研究可能为 PCa 提供一种新的治疗策略。

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