糠酸莫米松通过激活骨肉瘤中的 AMPK/mTOR 信号通路抑制肿瘤进展并促进细胞凋亡

IF 3.4 2区 医学 Q2 Medicine Journal of Bone Oncology Pub Date : 2024-06-29 DOI:10.1016/j.jbo.2024.100618
Zhaohui Li , Xiang Fei , Zhen Pan , Yonghui Liang , Qingcheng Yang , Dongdong Cheng
{"title":"糠酸莫米松通过激活骨肉瘤中的 AMPK/mTOR 信号通路抑制肿瘤进展并促进细胞凋亡","authors":"Zhaohui Li ,&nbsp;Xiang Fei ,&nbsp;Zhen Pan ,&nbsp;Yonghui Liang ,&nbsp;Qingcheng Yang ,&nbsp;Dongdong Cheng","doi":"10.1016/j.jbo.2024.100618","DOIUrl":null,"url":null,"abstract":"<div><p>Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma <em>in vitro</em> and <em>in vivo</em>. <em>In vitro</em>, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively<em>. In vivo</em>, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. <em>In vivo</em>, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway <em>in vitro</em> and <em>in vivo</em>, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"47 ","pages":"Article 100618"},"PeriodicalIF":3.4000,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000988/pdfft?md5=053589ba6cad63a6290788b17e441a8e&pid=1-s2.0-S2212137424000988-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Mometasone furoate inhibits tumor progression and promotes apoptosis through activation of the AMPK/mTOR signaling pathway in osteosarcoma\",\"authors\":\"Zhaohui Li ,&nbsp;Xiang Fei ,&nbsp;Zhen Pan ,&nbsp;Yonghui Liang ,&nbsp;Qingcheng Yang ,&nbsp;Dongdong Cheng\",\"doi\":\"10.1016/j.jbo.2024.100618\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma <em>in vitro</em> and <em>in vivo</em>. <em>In vitro</em>, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively<em>. In vivo</em>, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. <em>In vivo</em>, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway <em>in vitro</em> and <em>in vivo</em>, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.</p></div>\",\"PeriodicalId\":48806,\"journal\":{\"name\":\"Journal of Bone Oncology\",\"volume\":\"47 \",\"pages\":\"Article 100618\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-06-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2212137424000988/pdfft?md5=053589ba6cad63a6290788b17e441a8e&pid=1-s2.0-S2212137424000988-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Bone Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212137424000988\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bone Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212137424000988","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

骨肉瘤是青少年最常见的原发性恶性骨肿瘤。虽然骨肉瘤的治疗方法有所改善,但三十年来总体生存率却没有变化,因此需要开发新的治疗靶点。最近,有报道称糖皮质激素具有抗肿瘤作用。糠酸莫美他松(MF)是一种人工合成的糖皮质激素,具有很高的临床应用价值,但有关其抗肿瘤作用的报道却很少。在此,我们验证了糠酸莫美他松在体外和体内对骨肉瘤的作用。在体外,我们使用细胞计数试剂盒-8(CCK-8)、集落形成、流式细胞术、伤口愈合和透孔试验分别检测了细胞增殖、细胞周期进展、细胞凋亡和细胞转移。在体内,我们建立了异种移植小鼠模型。为了研究 AMPK 通路的潜在作用,我们使用了 AMPK 特异性抑制剂(多索吗啡)。免疫组化和 Western 印迹法评估了细胞周期、细胞凋亡和 AMPK/mTOR 通路激活相关因子的表达水平。MF以剂量依赖性方式抑制骨肉瘤细胞的增殖和转移,并诱导其S期停滞和凋亡。在体内,MF能有效抑制骨肉瘤细胞的生长和肺转移,但对内脏器官无不良影响。此外,MF 还能激活骨肉瘤的 AMPK/mTOR 通路。多索吗啡能明显减弱 MF 诱导的抗肿瘤活性。综上所述,MF可在体外和体内通过AMPK/mTOR信号通路抑制骨肉瘤的增殖和转移,促进骨肉瘤细胞的凋亡,为后续骨肉瘤治疗的学术和临床研究提供了新的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Mometasone furoate inhibits tumor progression and promotes apoptosis through activation of the AMPK/mTOR signaling pathway in osteosarcoma

Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma in vitro and in vivo. In vitro, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively. In vivo, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. In vivo, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway in vitro and in vivo, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
相关文献
二甲双胍通过HDAC6和FoxO3a转录调控肌肉生长抑制素诱导肌肉萎缩
IF 8.9 1区 医学Journal of Cachexia, Sarcopenia and MusclePub Date : 2021-11-02 DOI: 10.1002/jcsm.12833
Min Ju Kang, Ji Wook Moon, Jung Ok Lee, Ji Hae Kim, Eun Jeong Jung, Su Jin Kim, Joo Yeon Oh, Sang Woo Wu, Pu Reum Lee, Sun Hwa Park, Hyeon Soo Kim
具有疾病敏感单倍型的非亲属供体脐带血移植后的1型糖尿病
IF 3.2 3区 医学Journal of Diabetes InvestigationPub Date : 2022-11-02 DOI: 10.1111/jdi.13939
Kensuke Matsumoto, Taisuke Matsuyama, Ritsu Sumiyoshi, Matsuo Takuji, Tadashi Yamamoto, Ryosuke Shirasaki, Haruko Tashiro
封面:蛋白质组学分析确定IRSp53和fastin是PRV输出和直接细胞-细胞传播的关键
IF 3.4 4区 生物学ProteomicsPub Date : 2019-12-02 DOI: 10.1002/pmic.201970201
Fei-Long Yu, Huan Miao, Jinjin Xia, Fan Jia, Huadong Wang, Fuqiang Xu, Lin Guo
来源期刊
CiteScore
7.20
自引率
2.90%
发文量
50
审稿时长
34 days
期刊介绍: The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.
期刊最新文献
Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway. Using β-Elemene to reduce stemness and drug resistance in osteosarcoma: A focus on the AKT/FOXO1 signaling pathway and immune modulation. Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS. Mixed reality infrastructure based on deep learning medical image segmentation and 3D visualization for bone tumors using DCU-Net. Determinants of tumor necrosis and its impact on outcome in patients with Localized osteosarcoma uniformly treated with a response adapted regimen without high dose Methotrexate– A retrospective institutional analysis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1