CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.

Autor: Cui Z; Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Xu D; Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450003, Henan, China., Zhang F; Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Sun J; Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Song L; Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Ye W; Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Zeng J; Department of Laboratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China., Zhou M; Department of Respiratory Medicine, Jinshan Branch of the Sixth People's Hospital of Shanghai, Shanghai Jiaotong University, China., Ruan Z; Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China., Zhang L; Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address: zhanglinlin@xinhuamed.com.cn., Ren R; Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address: renrongrong@xinhuamed.com.cn.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2021 Aug 15; Vol. 405 (2), pp. 112677. Date of Electronic Publication: 2021 Jun 07.
DOI: 10.1016/j.yexcr.2021.112677
Abstrakt: Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8 + T cells, and cytokines (tumor growth factor (TGF)-β, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE