Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages.
Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages.
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禁食通过减少肿瘤相关巨噬细胞的 M2 极化来抑制结直肠癌的生长
DOI：
10.18632/oncotarget.20301
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发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Miao C
中科院分区：
文献类型：
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作者：
Sun P;Wang H;He Z;Chen X;Wu Q;Chen W;Sun Z;Weng M;Zhu M;Ma D;Miao C
饮食限制已被公认为癌症的健康和自然疗法。据报道，不同形式的限食可以促进抗肿瘤免疫。然而，目前尚不清楚禁食如何影响肿瘤相关巨噬细胞（TAM）。本研究旨在探讨禁食与肿瘤相关巨噬细胞抗肿瘤免疫的关系。在体内，结果显示隔日禁食2周可抑制小鼠肿瘤生长，而不会导致体重减轻。隔日禁食组肿瘤组织中肿瘤相关巨噬细胞的M2极化也降低。在体外实验中，禁食诱导CT 26细胞自噬，通过抑制CT 26细胞CD 73的表达，减少细胞外腺苷的产生。在禁食状态下，腺苷减少可通过阻断JAK 1/STAT 3信号通路抑制RAW264.7细胞的M2极化。最终，CT 26癌细胞的增殖由于禁食促进的抗肿瘤免疫而下降。这些结果表明，禁食抑制M2极化的肿瘤相关的巨噬细胞抑制肿瘤生长，通过降低腺苷水平在体内和体外的肿瘤微环境。这一过程与肿瘤细胞的自噬增加有关。
Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells.