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

Qingmin Sun; Mengyun Yuan; Hongxing Wang; Xingxing Zhang; Ruijuan Zhang; Haidan Wang; Xu Chen; Min Zhu; Shenlin Liu; Jian Wu

doi:10.3389/fonc.2021.767116

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

Front Oncol. 2021 Dec 2:11:767116. doi: 10.3389/fonc.2021.767116. eCollection 2021.

Authors

Qingmin Sun¹, Mengyun Yuan^{1

2}, Hongxing Wang^{1

2}, Xingxing Zhang¹, Ruijuan Zhang^{1

2}, Haidan Wang¹, Xu Chen^{1

2}, Min Zhu¹, Shenlin Liu¹, Jian Wu¹

Affiliations

¹ Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
² No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

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).

Keywords: PKM2; aerobic glycolysis; cancer metabolism; gastric cancer; traditional Chinese medicine.