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Quercetin encapsulated in folic acid-modified liposomes is therapeutic against osteosarcoma by non-covalent binding to the JH2 domain of JAK2 Via the JAK2-STAT3-PDL1.
Jing, Doudou; Wu, Wei; Chen, Xuanzuo; Xiao, Hongwei; Zhang, Zhenhao; Chen, Fengxia; Zhang, Zhicai; Liu, Jianxiang; Shao, Zengwu; Pu, Feifei.
Afiliação
  • Jing D; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China; Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: dg142625@163.com.
  • Wu W; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: waynewu@hust.edu.cn.
  • Chen X; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: huentso@outlook.com.
  • Xiao H; Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan, Hubei 430064, PR China. Electronic address: xiaohongwei2003@163.com.
  • Zhang Z; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: m202075884@hust.edu.cn.
  • Chen F; Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, PR China. Electronic address: fengxiachen@whu.edu.cn.
  • Zhang Z; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: 2010XH0880@hust.edu.cn.
  • Liu J; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: liujianxiangljx@163.com.
  • Shao Z; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: shaozengwupro@163.com.
  • Pu F; Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address: pufeifei@hust.edu.cn.
Pharmacol Res ; 182: 106287, 2022 08.
Article em En | MEDLINE | ID: mdl-35671921
Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Limite: Adolescent / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Osteossarcoma Limite: Adolescent / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article