PUBLICATION
Electroacupuncture Facilitates Vascular Normalization by Inhibiting Glyoxalase1 in Endothelial Cells to Attenuate Glycolysis and Angiogenesis in Triple-Negative Breast Cancer
- Authors
- Wan, Y.X., Qi, X.W., Lian, Y.Y., Liu, Z.Y., Wang, H., Qiu, Y.Q., Zhang, C.G., Li, W.N., Jiang, H.L., Yang, D.H., Zhao, W., Chen, Z.S., Huang, J.C.
- ID
- ZDB-PUB-240701-8
- Date
- 2024
- Source
- Cancer letters 598: 217094 (Journal)
- Registered Authors
- Keywords
- Acupuncture, Glyoxalase 1(GLO1), Methylglyoxal-glycolytic pathway, Triple-Negative Breast Cancer, Vascular Normalization
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Proliferation
- Electroacupuncture*/methods
- Endothelial Cells/metabolism
- Female
- Glycolysis*
- Human Umbilical Vein Endothelial Cells
- Humans
- Lactoylglutathione Lyase*/genetics
- Lactoylglutathione Lyase*/metabolism
- Mice
- Mice, Inbred BALB C
- Neovascularization, Pathologic*/metabolism
- Paclitaxel/pharmacology
- Pyruvaldehyde/metabolism
- Triple Negative Breast Neoplasms*/genetics
- Triple Negative Breast Neoplasms*/metabolism
- Triple Negative Breast Neoplasms*/pathology
- Triple Negative Breast Neoplasms*/therapy
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 38945204 Full text @ Cancer Lett.
Citation
Wan, Y.X., Qi, X.W., Lian, Y.Y., Liu, Z.Y., Wang, H., Qiu, Y.Q., Zhang, C.G., Li, W.N., Jiang, H.L., Yang, D.H., Zhao, W., Chen, Z.S., Huang, J.C. (2024) Electroacupuncture Facilitates Vascular Normalization by Inhibiting Glyoxalase1 in Endothelial Cells to Attenuate Glycolysis and Angiogenesis in Triple-Negative Breast Cancer. Cancer letters. 598:217094.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping