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Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer
Liu, Xinkui1; Bai, Meirong2; Li, Huiying3; Ye, Peizhi4; Duan, Xiaoxia5; Wu, Chao1; Huang, Zhihong1; Lu, Shan1; Zhang, Jingyuan1; Zhao, Zihan1; Guo, Fengying6; You, Rongli7; Qin, Wenjie7; Wang, Wei7; Han, Aiqing6; Shen, Liangliang1; Wang, Yitao8; Zhao, Zheng5; Luo, Hua8; Wu, Jiarui1
2022-10-31
Source PublicationFrontiers in Immunology
Volume13
AbstractBackground: Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. Methods: A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. Results: CKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8 T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8 T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro. Conclusions: The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.
Keyword4T1 tumor bearing mice compound kushen injection single cell RNA-sequencing T lymphocytes triple-negative breast cancer
DOI10.3389/fimmu.2022.965342
URLView the original
Language英語English
Scopus ID2-s2.0-85142038765
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, China
2.Key Laboratory of Mongolian Medicine Research and Development Engineering, Ministry of Education, Tongliao, China
3.College of Biological Sciences and Technology, Beijing Key Laboratory of Food Processing and Safety in Forestry, Beijing Forestry University, Beijing, China
4.National Cancer Center, National Clinical Research Center for Cancer, Chinese Medicine Department of the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
5.Beijing Zest Bridge Medical Technology Inc, Beijing, China
6.School of Management, Beijing University of Chinese Medicine, Beijing, China
7.Beijing Zhendong Pharmaceutical Research Institute Co., Ltd, Beijing, China
8.Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
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Liu, Xinkui,Bai, Meirong,Li, Huiying,et al. Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer[J]. Frontiers in Immunology,2022,13.
APA Liu, Xinkui,Bai, Meirong,Li, Huiying,Ye, Peizhi,Duan, Xiaoxia,Wu, Chao,Huang, Zhihong,Lu, Shan,Zhang, Jingyuan,Zhao, Zihan,Guo, Fengying,You, Rongli,Qin, Wenjie,Wang, Wei,Han, Aiqing,Shen, Liangliang,Wang, Yitao,Zhao, Zheng,Luo, Hua,&Wu, Jiarui.(2022).Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer.Frontiers in Immunology,13.
MLA Liu, Xinkui,et al."Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer".Frontiers in Immunology 13(2022).
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