Department of Reproductive Medicine, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou City, China.
Gynecol Endocrinol. 2023 Aug 2;39(1):2244600. doi: 10.1080/09513590.2023.2244600.
Polycystic ovarian syndrome (PCOS) is a prevalent gynecologic disorder, often associated with abnormal follicular development. Cangfu Daotan decoction (CFD) is a traditional Chinese medicine formula that is effective in alleviating PCOS clinically, but the specific mechanism remains unclear. Forkhead box K1 (FOXK1) is associated with cellular function. This study aimed to explore the effects of CFD and FOXK1 on PCOS. High-fat diet and letrozole were combined to establish PCOS rat models. Next, primary GCs were extracted from those PCOS rats. Then, GC cells were transfected with si-FOXK1 or oe-FOXK1. CFD-contain serum was prepared, and experiments were conducted to investigate the regulation of FOXK1 by CFD. FOXK1 was highly expressed in GCs of PCOS rats. Further investigation revealed that FOXK1 overexpression resulted in inhibition of proliferation and DNA synthesis, along with promotion of apoptosis and autophagy in GCs. Additionally, it was found that FOXK1 promoted the expressions of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway-related proteins. Interestingly, treatment with CFD reversed all the effects of FOXK1 overexpression in GCs. This study demonstrated that CFD exerted a protective role in PCOS by inhibiting FOXK1, which provided a research basis for the application of CFD in PCOS, and suggested that FOXK1 is a novel therapeutic target in PCOS treatment.
多囊卵巢综合征(PCOS)是一种常见的妇科疾病,常伴有卵泡发育异常。苍附导痰汤(CFD)是一种有效的中药方剂,临床上可缓解 PCOS,但具体机制尚不清楚。叉头框 K1(FOXK1)与细胞功能有关。本研究旨在探讨 CFD 和 FOXK1 对 PCOS 的影响。采用高脂饮食联合来曲唑建立 PCOS 大鼠模型。提取 PCOS 大鼠的原代 GC,然后转染 si-FOXK1 或 oe-FOXK1。制备 CFD 含血清,进行实验以研究 CFD 对 FOXK1 的调节。FOXK1 在 PCOS 大鼠的 GC 中高表达。进一步研究发现,FOXK1 过表达抑制 GC 的增殖和 DNA 合成,促进 GC 的凋亡和自噬。此外,还发现 FOXK1 促进了 AMP 激活的蛋白激酶(AMPK)/雷帕霉素靶蛋白(mTOR)通路相关蛋白的表达。有趣的是,CFD 治疗逆转了 FOXK1 过表达在 GC 中的所有作用。本研究表明,CFD 通过抑制 FOXK1 对 PCOS 发挥保护作用,为 CFD 在 PCOS 中的应用提供了研究基础,并提示 FOXK1 是 PCOS 治疗的新靶点。