Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages

Abstract

// Pengfei Sun 1, * , Huihui Wang 1, * , Zhiyong He 1, * , Xiangyuan Chen 1 , Qichao Wu 1 , Wankun Chen 1 , Zhirong Sun 1 , Meilin Weng 1 , Minmin Zhu 1 , Duan Ma 2 and Changhong Miao 1 1 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Changhong Miao, email: miaochh@aliyun.com Duan Ma, email: duanma@fudan.edu.cn Keywords: fasting, tumor-associated macrophages, colorectal cancer, adenosine, autophagy Received: May 24, 2017     Accepted: June 30, 2017     Published: August 16, 2017 ABSTRACT 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.