摘要
犬乳腺肿瘤(CMT)是母犬癌症相关死亡的最常见疾病因素之一,因其高复发性和转移性导致传统手术疗法面临挑战。天然化合物橄榄苦苷Ole与多种现象,如寿命延长、降低疾病发病率和死亡率密切相关,然而其对CMT的影响尚不清楚。因此,本研究开展了以下试验以探究Ole是否对犬乳腺肿瘤的发展产生影响:利用划痕试验、流式细胞术、RT-qPCR和蛋白免疫印迹等技术,检测不同浓度的Ole对CHMm细胞的活力、迁移能力、凋亡及相应蛋白Bax和BCL-2的表达水平和肿瘤相关基因mRNA的表达等情况的影响,同时探究其作用机制。结果显示,将Ole作用CMT细胞CHMm后,其激活了PI3K/AKT信号通路,诱导了相关蛋白的磷酸化,显著抑制了p-PI3K和p-AKT蛋白的表达水平。同时,Ole显著抑制了CMT细胞的存活、迁移和增殖能力。此外,与细胞凋亡密切相关的蛋白Bax和BCL-2的表达以及一些与肿瘤相关的基因mRNA的表达均受到了显著的调控,表明Ole介导PI3K/AKT信号通路有效诱导了CMT细胞的凋亡。这一研究提示Ole有望成为治疗乳腺癌的关键药物,同时为开发出针对CMT的有效治疗方法提供了关键的靶点。
Canine mammary tumors are one of the most common causes of cancer-related death in female dogs,challenging traditional surgical therapies due to their high recurrence and metastasis.The natural compound Ole is strongly associated with a variety of phenomena,such as increased longevity,reduced disease incidence and mortality.However,its effect on canine mammary tumors is unclear.Therefore,the following experiments were conducted to investigate whether Ole has an effect on the development of canine mammary tumors:The effects of Ole at different concentra-tions on CHMm cell viability,migration ability,apoptosis,expression levels of corresponding pro-teins Bax and BCL-2 and mRNA expression of tumor-related genes were detected by scratch test,flow cytometry,RT-qPCR and protein western blot,and the mechanism of action was also ex-plored.The results showed that Ole activated the PI3K/AKT signaling pathway,induced phospho-rylation of related proteins,and significantly inhibited the expression levels of p-PI3K and p-AKT after applying OLE to CHMm of canine mammary tumor cells.At the same time,Ole significantly inhibited the survival,migration and proliferation of canine mammary tumor cells.In addition,the expressions of proteins Bax and BCL-2,which are closely related to apoptosis,and mRNA expres-sions of some tumor-related genes were significantly regulated,suggesting that Ole mediated PI3K/AKT signaling pathway effectively induced apoptosis of canine mammary tumor cells.This study suggests that Ole has the potential to become a key drug in the treatment of mammary canc-er,and provides a key target for the development of effective therapies against canine mammary tumors.
作者
叶彦
张玉珠
杜崇涛
谢光洪
郑慧华
YE Yan;ZHANG Yuzhu;DU Chongtao;XIE Guanghong;ZHENG Huihua(College of Veterinary Medicine,Jilin University,Changchun 130062,China;Dr.Xie Animal Hospital,Changchun 130062,China;School of Animal Medicine,College of Animal Science and Technology,Zhejiang Agriculture and Forestry University,Hangzhou 311300,China)
出处
《中国兽医学报》
北大核心
2025年第11期2466-2473,共8页
Chinese Journal of Veterinary Science
基金
国家自然科学基金资助项目(32273075)
吉林省科技发展计划项目(20230505032ZP)。
