Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

• Main Authors: Cheng Qian (Author), Yueke Zhou (Author), Teng Zhang (Author), Guanglu Dong (Author), Mengyao Song (Author), Yu Tang (Author), Zhonghong Wei (Author), Suyun Yu (Author), Qiuhong Shen (Author), Wenxing Chen (Author), Jaesung P. Choi (Author), Juming Yan (Author), Chongjin Zhong (Author), Li Wan (Author), Jia Li (Author), Aiyun Wang (Author), Yin Lu (Author), Yang Zhao (Author)
• Format: Book
• Published: Elsevier, 2024-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 progression. Herein, 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 agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

Item Description

2211-3835
10.1016/j.apsb.2024.02.003