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: Qingmin Sun, Mengyun Yuan, Hongxing Wang, Xingxing Zhang, Ruijuan Zhang, Haidan Wang, Xu Chen, Min Zhu, Shenlin Liu, Jian Wu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/70cf44ee81a641ff9899aba70027aa18
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spelling oai:doaj.org-article:70cf44ee81a641ff9899aba70027aa182021-12-02T11:06:52ZPKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression2234-943X10.3389/fonc.2021.767116https://doaj.org/article/70cf44ee81a641ff9899aba70027aa182021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.767116/fullhttps://doaj.org/toc/2234-943XGastric 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 ArticleRutin (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).Qingmin SunMengyun YuanMengyun YuanHongxing WangHongxing WangXingxing ZhangRuijuan ZhangRuijuan ZhangHaidan WangXu ChenXu ChenMin ZhuShenlin LiuJian WuFrontiers Media S.A.articletraditional Chinese medicinePKM2gastric canceraerobic glycolysiscancer metabolismNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic traditional Chinese medicine
PKM2
gastric cancer
aerobic glycolysis
cancer metabolism
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle traditional Chinese medicine
PKM2
gastric cancer
aerobic glycolysis
cancer metabolism
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Qingmin Sun
Mengyun Yuan
Mengyun Yuan
Hongxing Wang
Hongxing Wang
Xingxing Zhang
Ruijuan Zhang
Ruijuan Zhang
Haidan Wang
Xu Chen
Xu Chen
Min Zhu
Shenlin Liu
Jian Wu
PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
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 ArticleRutin (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).
format article
author Qingmin Sun
Mengyun Yuan
Mengyun Yuan
Hongxing Wang
Hongxing Wang
Xingxing Zhang
Ruijuan Zhang
Ruijuan Zhang
Haidan Wang
Xu Chen
Xu Chen
Min Zhu
Shenlin Liu
Jian Wu
author_facet Qingmin Sun
Mengyun Yuan
Mengyun Yuan
Hongxing Wang
Hongxing Wang
Xingxing Zhang
Ruijuan Zhang
Ruijuan Zhang
Haidan Wang
Xu Chen
Xu Chen
Min Zhu
Shenlin Liu
Jian Wu
author_sort Qingmin Sun
title 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_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_sort pkm2 is the target of a multi-herb-combined decoction during the inhibition of gastric cancer progression
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/70cf44ee81a641ff9899aba70027aa18
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