Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ

Autor: Mengyun Yuan, Hongxing Wang, Jian Wu, Min Zhu, Qingmin Sun, Haidan Wang, Xiaodong Xie, Shenlin Liu, Xin-Tian Xu, Xi Zou
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Epithelial-Mesenchymal Transition
THP-1 Cells
Traditional Chinese medicine
RM1-950
PI3Kγ
Metastasis
03 medical and health sciences
Mice
0302 clinical medicine
In vivo
Cell Movement
Stomach Neoplasms
medicine
Tumor Microenvironment
Macrophage
Animals
Class Ib Phosphatidylinositol 3-Kinase
Humans
Neoplasm Metastasis
Protein Kinase Inhibitors
Pharmacology
business.industry
Tumor-associated macrophages
Cancer
Cell Differentiation
General Medicine
medicine.disease
Antineoplastic Agents
Phytogenic
In vitro
Immune checkpoint
Coculture Techniques
030104 developmental biology
Phenotype
030220 oncology & carcinogenesis
Cancer research
Disease Progression
Cytokines
Therapeutics. Pharmacology
Inflammation Mediators
business
Gastric cancer
Reprogramming
Jian-pi-yang-zheng decoction
Drugs
Chinese Herbal
Signal Transduction
Zdroj: Biomedicine & Pharmacotherapy, Vol 129, Iss, Pp 110440-(2020)
ISSN: 0753-3322
Popis: Jian-pi-yang-zheng Decoction (JPYZ) is a traditional Chinese medicine that is used for the treatment of advanced gastric cancer, and it shows good efficacy in patients. A previous study indicated that JPYZ inhibited the progression of gastric cancer via the regulation of tumor-associated macrophages (TAMs), but the underlying molecular target of JPYZ regulation of TAMs has not been determined. The present study used modified-JPYZ (mJPYZ) to extend our investigation of gastric cancer. Our results showed that mJPYZ inhibited gastric cancer progression in vivo and in vitro. We found that mJPYZ decreased the activity of PI3-kinase γ (PI3Kγ) in TAMs, reduced the anti-inflammatory factor IL-10 and increased the expression of pro-inflammatory cytokines, such as TNF-α and IL-1β, which ultimately promoted the conversion of TAMs from M2 to M1. Our findings also indicated that mJPYZ inhibited the growth and metastasis of gastric cancer by alleviating the unfavorable differentiation of TAMs via the PI3Kγ signaling cascades. In conclusion, the present findings indicated that mJPYZ inhibited gastric cancer cell EMT via PI3Kγ-dependent TAM reprogramming, which eventually suppressed gastric cancer growth and metastasis. Our study provides an underlying mechanism of a Chinese medicine in the treatment of gastric cancer via PI3Kγ in macrophages.
Databáze: OpenAIRE
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