Acertannin通过抑制C57BL/6J小鼠结肠表达白细胞介素-1β,单核细胞趋化蛋白-1,环氧合酶-2和胸腺细胞选择相关高迁移率群体(TOX)/TOX2,预防了azoxymethane / dextran sulfate sodium引起的结肠癌生长。
Acertannin prevents azoxymethane/dextran sulfate sodium-induced colon cancer growth by inhibiting the colonic expression of interleukin-1β, monocyte chemoattractant protein-1, cyclooxygenase-2, and thymocyte selection-associated high mobility group box proteins (TOX)/TOX2 in C57BL/6J mice.
发表日期:2023 Mar 27
作者:
Yoshiyuki Kimura, Masahiko Taniguchi, Takuo Okuda
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
结直肠癌是2019年与癌症相关死亡的第二大原因。本文研究了含有acertannin的枫属植物对azoxymethane(AOM)/dextran酸钠(DDS)诱导的结直肠癌生长和结肠内白细胞介素(IL)-1β、单核细胞趋化蛋白(MCP)-1、IL-10和程序性细胞死亡-1(PD-1)水平的影响。肠道癌症的诱发是通过腹腔注射AOM(10 mg/kg)在第0和第27天进行的。小鼠在第7-14天、第32-33天和第35-38天可饮用1%(w/v)的DDS饮用水。Acertannin(30和100 mg/kg)在第1-16天口服,第16-26天停止,然后在第27-41天再次口服。使用相应的ELISA试剂盒测量细胞因子、趋化因子和PD-1的结肠水平。与未受Acertannin治疗的小鼠相比,受Acertannin治疗的小鼠瘤体数和面积分别减少了53.9%和63.1%。此外,IL-1β、MCP-1、IL-10和PD-1的结肠水平分别减少了57.3%、62.9%、62.8%和100%,而Cox-2、TOX/TOX2、PD-1和STAT3磷酸化阳性细胞数量分别减少了79.6%、77.9%、93.8%和100%。综上所述,Acertannin对AOM/DSS诱导的结直肠肿瘤生长的抑制作用似乎与结肠内IL-1β、MCP-1、IL-10和PD-1水平的降低有关,通过在肿瘤微环境中下调COX-2和TOX/TOX2的表达实现。版权所有©2023 Elsevier B.V.出版。
Colon cancer was the second leading cause of cancer-related death in 2019. We herein investigated the effects of acertannin containing Acer species on azoxymethane (AOM)/dextran sulfate sodium (DDS)-induced colon cancer growth and changes in the colonic levels of interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1). Colorectal carcinogenesis was induced by an intraperitoneal injection of AOM (10 mg/kg) on days 0 and 27. Mice were given 1% (w/v) DSS drinking water ad libitum on days 7-14, 32-33, and 35-38. Acertannin (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16-26), and then administered again on days 27-41. The colonic levels of cytokines, a chemokine, and PD-1 were measured using the respective ELISA kits. The number and area of tumors in mice treated with acertannin (100 mg/kg) decreased by 53.9 and 63.1%, respectively. Furthermore, the colonic levels of IL-1β, MCP-1, IL-10, and PD-1 showed reductions of 57.3, 62.9, 62.8, and 100%, respectively, while the numbers of cyclooxygenase-2 (COX-2)-, thymocyte selection-associated high mobility group box proteins (TOX)/TOX2-, PD-1-, and signal transducer and activator of transcription 3 (STAT3) phosphorylation-positive numbers decreased by 79.6, 77.9, 93.8, and 100%, respectively. In conclusion, the inhibitory effects of acertannin on AOM/DSS-induced colon tumor growth appear to be associated with reductions in the colonic levels of IL-1β, MCP-1, IL-10, and PD-1 through the down-regulated expression of COX-2 and TOX/TOX2 in the tumor microenvironment.Copyright © 2023. Published by Elsevier B.V.