The immunostimulatory effects and pro-apoptotic activity of rhCNB against Lewis lung cancer is mediated by Toll-like receptor 4
文献类型：期刊论文
| 作者 | Yang, Jinju1,2; Zhang, Hongwei1; Zhu, Ziwei1; Gao, Yadan1; Xiang, Benqiong1; Wei, Qun1 |
| 刊名 | CANCER MEDICINE
 |
| 出版日期 | 2019-08-01 |
| 卷号 | 8期号:9页码:4441-4453 |
| 关键词 | antitumor drug antitumor immunity innate immunity rhCNB Toll-like receptor 4 |
| ISSN号 | 2045-7634 |
| DOI | 10.1002/cam4.2158 |
| 英文摘要 | Background Recombinant human calcineurin B subunit (rhCNB) has been shown to be an immune-stimulatory protein promoting cytokine production and inducing phenotypic maturation of Dendritic cells (DCs). In vivo, it has good antitumor efficacy, and has potential as an antitumor drug. Exogenous rhCNB was found to be internalized into tumor cells via the Toll-like receptor 4 (TLR4) complex, but it was not known whether its immuno-modulatory and antitumor functions involved entry by this same route. Methods The production and secretion of the cytokines and chemokines in innate immune cells induced by rhCNB were determined by ELISA, and the expression of CD40, CD80, CD86, and MHCII was analyzed by FACs. Experimental Lewis lung cancer (LLC) model was prepared in C57 BL/6 wild-type (WT) mice, TLR4(-/-) mice or their littermates by the inoculation of LLCs in their right armpit, and then administrated daily intraperitoneal injections (0.2 mL) of normal saline, rhCNB 20 mg/kg, and rhCNB 40 mg/kg, respectively. Results Recombinant human calcineurin B subunit promoted the production of antitumor cytokines by innate immune cells, and culture supernatants of rhCNB-stimulated immune cells induced apoptosis of LLCs. In addition, rhCNB up-regulated CD40, CD80, CD86, and MHCII expression in macrophages and DCs in TLR4(+) cells but failed to do so in TLR4 deficient cells. rhCNB also induced the formation of CD4(+) and CD8(+)T cells in splenocytes from WT mice, but not from TLR4-deficient littermates. Intraperitoneal administration of WT C57BL/6 mice with rhCNB resulted in a 50% reduction in LLC tumor growth, but failed to inhibit tumor growth in TLR4(-/-) littermates. Conclusions The in vivo antitumor and immunomodulatory effects of rhCNB are mediated by the TLR4. This conclusion is important for the further understanding and development of rhCNB as an antitumor drug. |
| WOS关键词 | CALCINEURIN B-SUBUNIT ; INNATE IMMUNITY ; TUMOR-CELLS ; AGONISTS ; PROTEIN ; RECOGNITION ; ENDOCYTOSIS ; ACTIVATION ; EXPRESSION ; LIGAND |
| 资助项目 | National Natural Science Foundation of China ; National Important Basic Research Project ; National Important Novel Medicine Research Project |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000478606700034 |
| 出版者 | WILEY |
| 资助机构 | National Natural Science Foundation of China ; National Important Basic Research Project ; National Important Novel Medicine Research Project |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/30322]  |
| 专题 | 中国科学院过程工程研究所 |
| 通讯作者 | Xiang, Benqiong; Wei, Qun |
| 作者单位 | 1.Beijing Normal Univ, Gene Engn & Biotechnol Beijing Key Lab, Dept Biochem & Mol Biol, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Jinju,Zhang, Hongwei,Zhu, Ziwei,et al. The immunostimulatory effects and pro-apoptotic activity of rhCNB against Lewis lung cancer is mediated by Toll-like receptor 4[J]. CANCER MEDICINE,2019,8(9):4441-4453. |
| APA | Yang, Jinju,Zhang, Hongwei,Zhu, Ziwei,Gao, Yadan,Xiang, Benqiong,&Wei, Qun.(2019).The immunostimulatory effects and pro-apoptotic activity of rhCNB against Lewis lung cancer is mediated by Toll-like receptor 4.CANCER MEDICINE,8(9),4441-4453. |
| MLA | Yang, Jinju,et al."The immunostimulatory effects and pro-apoptotic activity of rhCNB against Lewis lung cancer is mediated by Toll-like receptor 4".CANCER MEDICINE 8.9(2019):4441-4453. |
入库方式： OAI收割
来源：过程工程研究所
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