Electroacupuncture facilitates vascular normalization by inhibiting Glyoxalase1 in endothelial cells to attenuate glycolysis and angiogenesis in triple-negative breast cancer.

Autor: Wan YX; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Qi XW; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100029, China., Lian YY; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Liu ZY; Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Wang H; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Qiu YQ; The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China., Zhang CG; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Li WN; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Jiang HL; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China., Yang DH; New York College of Traditional Chinese Medicine, Mineola, NY, 11501, USA., Zhao W; Guanganmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, 100029, China., Chen ZS; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. Electronic address: chenz@stjohns.edu., Huang JC; The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: zryhhuang@163.com.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2024 Aug 28; Vol. 598, pp. 217094. Date of Electronic Publication: 2024 Jun 29.
DOI: 10.1016/j.canlet.2024.217094
Abstrakt: Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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