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PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates mod...

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Autores principales: Sun, Qingmin, Yuan, Mengyun, Wang, Hongxing, Zhang, Xingxing, Zhang, Ruijuan, Wang, Haidan, Chen, Xu, Zhu, Min, Liu, Shenlin, Wu, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675178/
https://www.ncbi.nlm.nih.gov/pubmed/34926270
http://dx.doi.org/10.3389/fonc.2021.767116
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author Sun, Qingmin
Yuan, Mengyun
Wang, Hongxing
Zhang, Xingxing
Zhang, Ruijuan
Wang, Haidan
Chen, Xu
Zhu, Min
Liu, Shenlin
Wu, Jian
author_facet Sun, Qingmin
Yuan, Mengyun
Wang, Hongxing
Zhang, Xingxing
Zhang, Ruijuan
Wang, Haidan
Chen, Xu
Zhu, Min
Liu, Shenlin
Wu, Jian
author_sort Sun, Qingmin
collection PubMed
description Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Rutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).
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spelling pubmed-86751782021-12-17 PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression Sun, Qingmin Yuan, Mengyun Wang, Hongxing Zhang, Xingxing Zhang, Ruijuan Wang, Haidan Chen, Xu Zhu, Min Liu, Shenlin Wu, Jian Front Oncol Oncology Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Rutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542). Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8675178/ /pubmed/34926270 http://dx.doi.org/10.3389/fonc.2021.767116 Text en Copyright © 2021 Sun, Yuan, Wang, Zhang, Zhang, Wang, Chen, Zhu, Liu and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sun, Qingmin
Yuan, Mengyun
Wang, Hongxing
Zhang, Xingxing
Zhang, Ruijuan
Wang, Haidan
Chen, Xu
Zhu, Min
Liu, Shenlin
Wu, Jian
PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title_full PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title_fullStr PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title_full_unstemmed PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title_short PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
title_sort pkm2 is the target of a multi-herb-combined decoction during the inhibition of gastric cancer progression
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675178/
https://www.ncbi.nlm.nih.gov/pubmed/34926270
http://dx.doi.org/10.3389/fonc.2021.767116
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