Dihydroxystilbenes prevent azoxymethane/dextran sulfate sodium-induced colon cancer by inhibiting colon cytokines, a chemokine, and programmed cell death-1 in C57BL/6J mice

被引:11
|
作者
Kimura, Yoshiyuki [1 ]
Sumiyoshi, Maho [1 ]
Kiyoi, Takeshi [2 ]
Baba, Kimiye [3 ]
机构
[1] Ehime Univ, Grad Sch Med, Dept Funct Biomed, Toon City, Ehime 7910295, Japan
[2] Ehime Univ, Adv Res Support Ctr ADRES, Div Analyt Biomed, Shigenobu Cho, Toon City, Ehime 7910295, Japan
[3] Osaka Univ Pharmaceut Sci, Dept Pharmacognosy, Takatsuki, Osaka 5691094, Japan
关键词
Colon cancer; Dihydroxystilbenes; IL-1; beta; PD-1; M2; macrophages; TUMOR-ASSOCIATED MACROPHAGES; CASSIA-GARRETTIANA HEARTWOOD; LUNG METASTASIS; ANTIMETASTATIC ACTIONS; GROWTH; RESVERATROL; DIFFERENTIATION; ACTIVATION; ANTITUMOR; ROOTS;
D O I
10.1016/j.ejphar.2020.173445
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The incidence of colon cancer increased worldwide in 2019 and its treatment is urgent from a quality of life perspective. A relationship has been reported between elevated numbers of tumor-associated macrophages (TAMs) in the tumor microenvironment and a poor prognosis in cancer patients, and M2 TAMs have been shown to promote tumor growth by immunosuppression through the stimulation of programmed death-1 (PD-1, an immune check point receptor), interleukin (IL)-1 beta, and monocyte chemoattractant protein (MCP)-1. We herein examined the effects of three synthetic dihydroxystilbenes (2,3-, 3,4-, and 4,4'-dihydroxystilbenes) on colon carcinogenesis, colon tumor growth, and colon cytokines (IL-1 beta, IL-6, and tumor necrosis factor (TNE)-alpha), a chemokine (MCP-1), vascular endothelial growth factor (VEGF), and PD-1 levels in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated C57BL/6J mice. The three dihydroxystilbenes inhibited colon carcinogenesis and tumor growth as well as increases in colon IL-1 beta, IL-6, MCP-1, and PD-1 levels in AOM/DDS-treated mice (in vivo). The three dihydroxystilbenes also suppressed COX-2 expression in colon tumors (in vivo). The results obtained also revealed that the three dihydroxystilbenes inhibited PD-1 elevations in M2-THP-1 macrophages (in vitro). Therefore, the inhibition of AOM/DSS-induced colon carcinogenesis and colon tumor growth by 2,3-, 3,4-, and 4,4'-dihydroxystilbenes appears to be due to the suppression of M2 TAM differentiation and activation and PD-1 expression (immunosuppression) via reductions in COX-2 expression levels in the colon tumor microenvironment.
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页数:19
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