中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery

文献类型：期刊论文

作者Long, Li1,2; Xiong, Wei1,2,3; Lin, Fenwang4; Hou, Jiazhen5; Chen, Guihua1,2,3; Peng, Taoxing2,3; He, Yihao2,3; Wang, Rui2,3; Xu, Qin1; Huang, Yongzhuo1,2,3,6
刊名JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
出版日期2023-05-10
卷号42期号:1页码:20
关键词Shikonin Colorectal cancer liver metastasis Glycolysis Pyruvate kinase M2 (PKM2) Epithelial-mesenchymal transition (EMT) Immune microenvironment
DOI10.1186/s13046-023-02688-z
通讯作者Xu, Qin(xuqin@gzucm.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要Background There are few effective medications for treating colorectal cancer and liver metastases (CRLM). The interactions among glycolysis, epithelial-mesenchymal transition (EMT), and immune microenvironment contribute to the progression of CRLM. A main glycolytic enzyme pyruvate Kinase M2 (PKM2) is highly expressed in colorectal cancer and CRLM, and thus can be a potential therapeutic target. Methods A therapeutic strategy was proposed and the shikonin-loaded and hyaluronic acid-modified MPDA nanoparticles (SHK@HA-MPDA) were designed for CRLM therapy via PKM2 inhibition for immunometabolic reprogramming. The treatment efficacy was evaluated in various murine models with liver metastasis of colorectal tumor. Results SHK@HA-MPDA achieved tumor-targeted delivery via hyaluronic acid-mediated binding with the tumorassociated CD44, and efficiently arrested colorectal tumor growth. The inhibition of PKM2 by SHK@HA-MPDA led to the remodeling of the tumor immune microenvironment and reversing EMT by lactate abatement and the suppression of TGF beta signaling; the amount of cytotoxic effector CD8+ T cells was increased while the immunosuppressive MDSCs decreased. Conclusion The work provided a promising targeted delivery strategy for CRLM treatment by regulating glycolysis, EMT, and anticancer immunity. [GRAPHICS] .
WOS关键词PYRUVATE-KINASE M2 ; LACTIC-ACID ; GENE-TRANSCRIPTION ; SUPPRESSOR-CELLS ; BETA-CATENIN ; TUMOR ; PKM2 ; BEVACIZUMAB ; MIGRATION ; BEHAVIOR
资助项目National Key Research and Development Program of China[2021YFC2400600] ; National Key Research and Development Program of China[2021YFE0103100] ; NFSC[81925035] ; National Foreign Expert Program[82050410361] ; Chinese Pharmaceutical Association-Yiling Joint Project[CPAYLJ201901] ; High-level new RD institute[2019B090904008] ; High-level Innovative Research Institute from Department of Science and Technology of Guangdong Province[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011]
WOS研究方向Oncology
语种英语
出版者BMC
WOS记录号WOS:000985909500001
源URL[http://119.78.100.183/handle/2S10ELR8/306614]  
专题新药研究国家重点实验室
通讯作者Xu, Qin; Huang, Yongzhuo
作者单位1.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China
4.Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Sch Clin Med, Dept Kidney Transplantat, Beijing, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Long, Li,Xiong, Wei,Lin, Fenwang,et al. Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2023,42(1):20.
APA Long, Li.,Xiong, Wei.,Lin, Fenwang.,Hou, Jiazhen.,Chen, Guihua.,...&Huang, Yongzhuo.(2023).Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,42(1),20.
MLA Long, Li,et al."Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 42.1(2023):20.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。