Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery
作者机构：Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia MedicaNanjing University of Chinese MedicineNanjing 210023China School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Centre for InflammationFaculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and MetabolismDepartment of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China Department of General SurgeryJiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical SchoolFaculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2024年第14卷第5期
页 面：2077-2096页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：This work was financially supported by the projects of National Natural Science Foundation of China(82003991,82101844,and 82304953) Natural Science Foundation of Jiangsu Province(BK20230744,China) Jiangsu Specially Appointed Professorship Foundation(013038021001,China) Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22-2045 and KYCX23-2038,China)
主 题：Salvianic acid A Tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin
摘 要：Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.
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