title: The involvement of M2 macrophage polarization inhibition in fenretinide-mediated chemopreventive effects on colon cancer.
abstract: Clinical studies have shown that fenretinide (4-HPR) is an attractive chemopreventive agent for cancer treatment. However, to date, few studies have demonstrated the mechanism of the preventive effect of 4-HPR. In our current study, we revealed that 4-HPR could significantly suppress IL-4/IL-13 induced M2-like polarization of macrophages, which was demonstrated by the reduced expression of M2 surface markers, the down-regulation of M2 marker genes, and the inhibition of M2-like macrophages promoted angiogenesis. Mechanistically, our study suggested that the inhibition of the phosphorylation of STAT6, rather than the generation of oxidative stress, is involved in the 4-HPR-driven inhibition of M2 polarization. More intriguingly, by utilizing adenomatous polyposis coli (APCmin/+) transgenic mice, we demonstrated that the tumorigenesis was dramatically decreased by 4-HPR treatment accompanied with fewer M2-like macrophages in the tumor tissues, thereby profoundly blocking tumor angiogenesis. These findings, for the first time, reveal the involvement of M2 polarization inhibition in 4-HPR-mediated chemoprevention, which provides a new point of insight and indicates the potential mechanism underlying the chemopreventive effect of 4-HPR.
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Dong
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Hangzhou First People's Hospital, Hangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Meng
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Meidan
authors.initials: M
authors.lastname: Ying
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: caoji88@zju.edu.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
authors.affiliation: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: yang924@zju.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D017313:Fenretinide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D017313:Fenretinide
keywords: 4-HPR; Cancer prevention; Colon cancer; STAT6; Tumor-associated macrophages