Dataset Information

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

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).

SUBMITTER: Sun Q

PROVIDER: S-EPMC8675178 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Sun Qingmin Q Yuan Mengyun M Wang Hongxing H Zhang Xingxing X Zhang Ruijuan R Wang Haidan H Chen Xu X Zhu Min M Liu Shenlin S Wu Jian J

Frontiers in oncology 20211202

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 reprogr ...[more]

PMID: 34926270

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Project description:Gastric cancer (GC) ranks as one of the most prevalent malignant tumors globally. The subtle manifestation of its early-stage symptoms often results in many GC patients being diagnosed at a late or advanced stage, thereby posing significant obstacles to the effectiveness of chemotherapy treatments. Therefore, identifying early biomarkers for GC is crucial. In recent years, an increasing number of studies have highlighted the pivotal role that aging plays in the progression of cancer. Among the various proteins involved, Cytoskeleton-associated protein 2 (CKAP2) emerges as a crucial player in controlling cell proliferation, regulating mitosis and cell division, and exerting a significant influence on the aging process. We employed a bioinformatics approach to assess the causal association between aging-related genes and GC and explore the potential significance of CKAP2 in GC by analyzing data sourced from various repositories, including Genotype Tissue Expression (GTEx), GWAS Catalog, The Database of Cell Senescence Genes (CellAge), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), and the Comparative Toxicology Genome Database (CTD). Our research summarized the causal relationship between CKAP2 expression and the development risk of GC, differential expression in GC, the relationship with the prognosis of GC, genetic correlation, functional analysis, and immune cell infiltration, and explored the interaction of CKAP2 and chemical substances. The findings revealed that an elevation in CKAP2 expression correlated with a reduced likelihood of developing GC. There was a significant difference in the expression of CKAP2 between GC and normal patients. Specifically, there was higher expression in GC compared to normal patients. In addition, CKAP2 has been proven to have diagnostic value in GC, and elevated levels of CKAP2 expression are indicative of a more favorable prognosis. Immune infiltration analysis revealed the relationship between CKAP2 and tumor immune microenvironment, while the Comparative Toxicology Genome Database (CTD) identified a small molecule compound that may target CKAP2. In summary, through comprehensive multivariate analyses, we identified and validated the potential role that CKAP2 may play in GC. Therefore, CKAP2 shows potential as an indicator for both the diagnosis and prognosis of GC, making it worthy of further clinical investigation.

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Dataset Information

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

Chemical compounds studied in this article

Publications

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

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