Jing Li1, Hongwei Cai2, Huihui Sun1, Jianbo Qu3, Bin Zhao2, Xuefeng Hu2, Wenjia Li2, Zhengming Qian2, Xia Yu1, Fenghua Kang1, Wenxuan Wang1, Zhenxin Zou1, Baohua Gu4, Kangping Xu5. 1. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China. 2. Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., LTD, Dongguan, 523850, China. 3. Center for Drug Evaluation, National Medical Products Administration, Beijing, 100022, China. 4. Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., LTD, Dongguan, 523850, China. Electronic address: baohua.gu@hec.cn. 5. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China. Electronic address: xukp395@csu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis is a traditional Chinese medicine. It is widely reported that Cordyceps sinensis has inhibitory effect on tumor growth and immunoregulation effect on macrophages. However, the exact mechanism of Cordyceps sinensis on macrophage polarization in tumor progression is not known. AIM OF STUDY: We aimed to investigate the role of extracts of Cordyceps sinensis on macrophage polarization and its underlying mechanism in antitumor activity. MATERIALS AND METHODS: The 4T1 orthotopic xenograft mouse model and immunohistochemical staining were used to investigate the effect of Cordyceps sinensis on breast tumor and the change of the macrophages phenotype in the tumor, respectively. A 3D co-culture assay was used to confirm the activity in vitro. Measurement of cytokines and NO, quantitative real-time PCR and flow cytometry assays were used to investigate the effect of Cordyceps sinensis on the macrophage polarization in vitro. The mechanism of the effect of Cordyceps sinensis on macrophages was investigated by using western blot assays. RESULTS: In the orthotopic mouse tumor model, Cordyceps sinensis inhibited the 4T1 tumor growth in a dose dependent manner, and the immunohistochemical staining analysis showed that there is a positive correlation between tumor growth inhibition and macrophage M1-like polarized phenotype. The cytokines and NO measurement, quantitative real-time PCR assay and flow cytometry assays confirmed that Cordyceps sinensis could promote macrophage differentiation toward the M1 phenotype. The 3D co-culture assay and western blot assay showed that Cordyceps sinensis could inhibit tumor growth by promoting macrophage polarization and enhance its activity by activating the NF-κB signaling pathway. CONCLUSION: These findings suggest that Cordyceps sinensis could potently suppress TNBC progression by promoting M1 phenotypic differentiation of macrophages via activation NF-κB signaling pathway in tumor microenvironment.
ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis is a traditional Chinese medicine. It is widely reported that Cordyceps sinensis has inhibitory effect on tumor growth and immunoregulation effect on macrophages. However, the exact mechanism of Cordyceps sinensis on macrophage polarization in tumor progression is not known. AIM OF STUDY: We aimed to investigate the role of extracts of Cordyceps sinensis on macrophage polarization and its underlying mechanism in antitumor activity. MATERIALS AND METHODS: The 4T1 orthotopic xenograft mouse model and immunohistochemical staining were used to investigate the effect of Cordyceps sinensis on breast tumor and the change of the macrophages phenotype in the tumor, respectively. A 3D co-culture assay was used to confirm the activity in vitro. Measurement of cytokines and NO, quantitative real-time PCR and flow cytometry assays were used to investigate the effect of Cordyceps sinensis on the macrophage polarization in vitro. The mechanism of the effect of Cordyceps sinensis on macrophages was investigated by using western blot assays. RESULTS: In the orthotopic mousetumor model, Cordyceps sinensis inhibited the 4T1 tumor growth in a dose dependent manner, and the immunohistochemical staining analysis showed that there is a positive correlation between tumor growth inhibition and macrophage M1-like polarized phenotype. The cytokines and NO measurement, quantitative real-time PCR assay and flow cytometry assays confirmed that Cordyceps sinensis could promote macrophage differentiation toward the M1 phenotype. The 3D co-culture assay and western blot assay showed that Cordyceps sinensis could inhibit tumor growth by promoting macrophage polarization and enhance its activity by activating the NF-κB signaling pathway. CONCLUSION: These findings suggest that Cordyceps sinensis could potently suppress TNBC progression by promoting M1 phenotypic differentiation of macrophages via activation NF-κB signaling pathway in tumor microenvironment.