Bufalin targets the SRC-3/MIF pathway in chemoresistant cells to regulate M2 macrophage polarization in colorectal cancer. (10th August 2021)

• Record Type: Journal Article
• Authors: Chen, Jinbao; Wang, Haijing; Jia, Linlin; He, Jing; Li, Yue; Liu, Huan; Wu, Ruixin; Qiu, Yanyan; Zhan, Yueping; Yuan, Zeting; Cao, Yijun; Li, Wei; Xu, Ke; Yin, Peihao
• Is Part Of: Cancer letters. Volume 513(2021)
• Page Start: 63
• Page End: 74
• Publication Date: 2021-08-10
• Subjects: Colorectal cancer -- Bufalin -- Oxaliplatin resistance -- SRC-3/MIF -- Tumour microenvironment; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.05.008
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: M2-polarized macrophages are one of critical factors in tumour chemoresistance. An increasing number of studies have shown that M2 macrophage polarization can be promoted by chemoresistance. A large number of evidences indicate that Bufalin has significant antitumour effect, previous studies have found that Bufalin can reduce the polarization of M2 macrophages to play an anti-tumour effect in vivo, but the mechanism remains unclear. In our study, we found that Bufalin reduced the polarization of M2 macrophages induced by chemoresistant cells both in vivo and in vitro; however, Bufalin had no obvious direct effect on M2 macrophage polarization. Furthermore, we demonstrated that Bufalin targeted the SRC-3 protein to reduce MIF release in chemoresistant cells in order to regulate the polarization of M2 macrophages. More interestingly, we also found that Cinobufacini, Bufalin is its main active monomer, which its could regulate the polarization of M2 macrophages to enhance the anti-tumour effect of oxaliplatin in vivo and in the clinic. Overall, this study provides a theoretical basis for the clinical application of drugs containing Bufalin as the main active ingredient in combination with established chemotherapy for the treatment of colorectal cancer. Highlights: Bufalin could reduce M2 macrophage polarization by regulating chemoresistant cells in vitro and in vivo. Bufalin could target SRC-3 to reduce MIF release in chemoresistant cells to regulate the polarization of M2 macrophages. Bufalin plays a crucial role in the anti-tumour efficacy of Cinobufacini in vivo and in the clinic as its major monomer.