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芍药新苷通过靶向 MUC1/Wnt/β-catenin 通路抑制卵巢癌转移。

Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/β‑catenin pathway.

机构信息

Department of Immunology and Microbiology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.

Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P.R. China.

出版信息

Int J Mol Med. 2024 Jul;54(1). doi: 10.3892/ijmm.2024.5384. Epub 2024 May 24.

Abstract

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial‑mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit‑8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S‑phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/β‑catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/β‑catenin pathway to induce anti‑metastatic, anti‑invasive and anti‑EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

摘要

卵巢癌 (OC) 是最常见的妇科恶性肿瘤之一。目前,化疗和放疗是 OC 的主要临床治疗方法;然而,它具有严重的副作用和高复发率。因此,迫切需要开发创新的治疗选择。牡丹酚(PFG)是从传统中药牡丹皮中分离得到的单萜化合物。PFG 可以抑制肿瘤细胞的增殖;然而,其对 OC 的抗癌活性尚未得到阐明。粘蛋白 1(MUC1)在各种恶性肿瘤中高度表达,与肿瘤增殖、转移和上皮间质转化(EMT)有关。此外,MUC1 影响肿瘤细胞中的许多信号通路。为了开发转移性 OC 的可能治疗方法,使用细胞计数试剂盒-8 测定法、Edu 测定法、流式细胞术、Transwell 测定法和 Western blot 分析研究了 PFG 在 OC 细胞中的抗肿瘤活性。此外,还评估了 PFG 如何影响 MUC1 的表达和功能。实验表明,PFG 显著抑制 OC 细胞增殖、迁移、侵袭和 EMT。PFG 还诱导 OC 细胞 S 期细胞周期停滞。此外,PFG 抑制 MUC1 启动子活性,导致 MUC1 蛋白表达减少。相比之下,MUC1 促进 OC 进展,包括细胞增殖、细胞周期进展和细胞迁移。OC 细胞中 MUC1 的稳定敲低增强了 PFG 阻断 Wnt/β-catenin 通路的能力,并限制了肿瘤细胞的侵袭和迁移,而 MUC1 的过表达部分抵消了 PFG 的抗肿瘤作用。综上所述,本研究表明 PFG 可能通过抑制 MUC1/Wnt/β-catenin 通路对 OC 发挥抗转移、抗侵袭和抗 EMT 作用。值得注意的是,MUC1 可能是 PFG 的直接靶标。因此,PFG 有望成为治疗 OC 的特异性抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5563/11188981/ca5c899b5da2/ijmm-54-01-05384-g00.jpg

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