High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression
High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression
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高剂量地塞米松在抗肿瘤进展中调控肿瘤微环境和内部代谢途径
DOI：
10.3390/ijms21051846
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发表时间：
2020-03
影响因子：
5.6
通讯作者：
Yajun Xie
中科院分区：
文献类型：
--
作者：
Lei Xu;Hua Xia;Dongsheng Ni;Yanxia Hu;Jianing Liu;Yao Qin;Qin Zhou;Qiying Yi;Yajun Xie
High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.
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影响因子：
1.6
作者：
Kumagai H;Kusaba H;Yamanaka T;Nio K;Inadomi K;Takayoshi K;Ito M;Tamura S;Makiyama A;Makiyama C;Hirano G;Shibata Y;Shirakawa T;Mitsugi K;Ariyama H;Esaki T;Akashi K;Baba E
通讯作者：
Baba E
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.5
作者：
Ma, Frank Y.;Han, Yingjie;Nikolic-Paterson, David J.
通讯作者：
Nikolic-Paterson, David J.
影响因子：
2
作者：
Yashu Xu;Cheng Yang;Shujun Zhang;Jiajun Li;Qing Xiao;Wenxiang Huang
通讯作者：
Yashu Xu;Cheng Yang;Shujun Zhang;Jiajun Li;Qing Xiao;Wenxiang Huang
DOI：
10.1016/j.critrevonc.2018.03.015
发表时间：
2018-06
期刊：
Critical reviews in oncology/hematology
影响因子：
--
作者：
C. Maurice-Dror;R. Perets;G. Bar-Sela
通讯作者：
C. Maurice-Dror;R. Perets;G. Bar-Sela