芍药甙元酮通过靶向 MUC1/Wnt/β-catenin 通路抑制卵巢癌转移

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2024-07-01 Epub Date: 2024-05-24 DOI:10.3892/ijmm.2024.5384
Qingling Liu, Liqin Jiang, Yun Zhao, Fang Su, Junfeng Li, Xinxin Tian, Wenhong Liu, Xiawei Jiang, Ye Xu, Fangfang Tao
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引用次数: 0

摘要

卵巢癌(OC)是最常见的妇科恶性肿瘤之一。目前,化放疗是卵巢癌的主要临床治疗方法,但其副作用大,复发率高。因此,迫切需要开发创新的治疗方案。芍药苷元酮(PFG)是从传统中药芍药中分离出来的单萜烯化合物。PFG 可抑制肿瘤细胞的增殖,但其对 OC 的抗癌活性尚未阐明。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 还影响肿瘤细胞的多种信号通路。为了开发一种治疗转移性卵巢癌的可能方法,研究人员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印迹分析法研究了PFG在卵巢癌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。实验结果表明,PFG 能显著抑制 OC 细胞的增殖、迁移、侵袭和 EMT。PFG 还能诱导 OC 细胞的 S 期细胞周期停滞。此外,PFG还抑制了MUC1启动子的活性,导致MUC1蛋白表达量减少。相比之下,MUC1促进了OC的进展,包括细胞增殖、细胞周期进展和细胞迁移。稳定敲除OC细胞中的MUC1能提高PFG阻断Wnt/β-catenin通路、限制肿瘤细胞侵袭和迁移的能力,而MUC1的过表达则部分抵消了PFG的抗肿瘤作用。总之,本研究表明,PFG可抑制MUC1/Wnt/β-catenin通路,从而诱导OC的抗转移、抗侵袭和抗EMT作用。值得注意的是,MUC1 可能是 PFG 的直接靶点。因此,PFG有望成为治疗OC的特异性抗肿瘤药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/β‑catenin pathway.

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.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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