Dou Lei, Yan Yan, Lu Enting, Li Fangmei, Tian Dongli, Deng Lei, Zhang Xue, Zhang Rongjin, Li Yin, Zhang Yi, Sun Ye
Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China.
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Transl Oncol. 2025 Feb;52:102244. doi: 10.1016/j.tranon.2024.102244. Epub 2024 Dec 10.
Cisplatin is the main chemotherapy drug for advanced ovarian cancer, but drug resistance often occurs. The aim of this study is to explore the molecular mechanism by which Guizhi Fuling capsule inhibits cisplatin resistance in ovarian cancer.
First, differences in cisplatin resistance, PA2G4 gene expression, migration, and invasion in A2780 cells and A2780/DDP cells were analyzed by qRT-PCR, scratch assay, transwell, immunofluorescence, and western blotting. Then, LC-MS/MS analysis of GFC chemical composition. qRT-PCR, scratch tests, transwell, pseudopodium formation, immunofluorescence, and western blotting were used to explore the mechanism by which GFC inhibited A2780/DDP cell migration and invasion. Finally, the anti-tumor efficacy of GFC was verified by in vivo experiments.
A2780/DDP cells had a greater ability to migrate and invade compared to their parents. Cell viability experiments showed that the migration and invasion ability of A278/DDP cells were significantly inhibited with the increase of GFC concentration. qRT-PCR results showed that compared with the blank control group, cisplatin group and GFC group, the transcription level of PA2G4 gene in the combination treatment group was significantly reduced. We also found that GFC combined with cisplatin inhibited the PI3K/AKT/GSK-3β signaling pathway by targeting PA2G4 gene expression, inhibited the epithelial-mesenchymal transition signaling pathway, decreased cell adhesion and inhibited the formation of cell pseudopodias.
GFC combined with cisplatin can target PA2G4 gene to regulate PI3K/AKT/GSK-3β Signaling pathway, inhibiting the invasion and migration of cisplatin resistant A2780/DDP cells in ovarian cancer.
顺铂是晚期卵巢癌的主要化疗药物，但常出现耐药。本研究旨在探讨桂枝茯苓胶囊抑制卵巢癌顺铂耐药的分子机制。
首先，通过qRT-PCR、划痕试验、Transwell、免疫荧光和蛋白质印迹法分析A2780细胞和A2780/DDP细胞在顺铂耐药性、PA2G4基因表达、迁移和侵袭方面的差异。然后，对桂枝茯苓胶囊进行LC-MS/MS化学成分分析。采用qRT-PCR、划痕试验、Transwell、伪足形成、免疫荧光和蛋白质印迹法探讨桂枝茯苓胶囊抑制A2780/DDP细胞迁移和侵袭的机制。最后，通过体内实验验证桂枝茯苓胶囊的抗肿瘤疗效。
与亲本细胞相比，A2780/DDP细胞具有更强的迁移和侵袭能力。细胞活力实验表明，随着桂枝茯苓胶囊浓度的增加，A278/DDP细胞的迁移和侵袭能力受到显著抑制。qRT-PCR结果显示，与空白对照组、顺铂组和桂枝茯苓胶囊组相比，联合治疗组PA2G4基因的转录水平显著降低。我们还发现，桂枝茯苓胶囊联合顺铂通过靶向PA2G4基因表达抑制PI3K/AKT/GSK-3β信号通路，抑制上皮-间质转化信号通路，降低细胞黏附并抑制细胞伪足的形成。
桂枝茯苓胶囊联合顺铂可靶向PA2G4基因调节PI3K/AKT/GSK-3β信号通路，抑制卵巢癌中顺铂耐药的A2780/DDP细胞的侵袭和迁移。
