Inhibition of curcumin on myeloid-derived suppressor cells is requisite for controlling lung cancer

被引:58
作者
Liu, Dan [1 ]
You, Ming [1 ]
Xu, Yujun [1 ]
Li, Fanlin [1 ]
Zhang, Dongya [1 ]
Li, Xiujun [1 ]
Hou, Yayi [1 ,2 ]
机构
[1] Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
[2] Jiangsu Key Lab Mol Med, Nanjing 210093, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Lung cancer; Curcumin; Myeloid-derived suppressor cells (MDSCs); TUMOR MICROENVIRONMENT; IMMUNE SUPPRESSION; SIGNALING PATHWAY; DNA-DAMAGE; MODEL; PROGRESSION; INFLAMMATION; MECHANISMS; EXPRESSION; CARCINOMA;
D O I
10.1016/j.intimp.2016.07.035
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lung cancer remains the leading cause of cancer mortality. Myeloid-derived suppressor cells (MDSCs) are potent immune-suppressive cells and present in most cancer patients. Recently, several studies have shown that curcumin inhibits the expansion of MDSCS in some cancers. However, it is not clear how curcumin modulates the suppressive function of MDSCs, and whether curcumin achieves anti-tumor effects via regulating the expansion of MDSCs in lung cancer. Here, our results showed that curcumin significantly inhibited tumor growth in a Lewis lung carcinoma (LLC) isogenic tumor model. Curcumin reduced the accumulation of MDSCs in spleen and tumor tissue in LLC isogenic model. And curcumin promoted the maturation and differentiation of MDSCs in tumor tissue. Notably, curcumin inhibited the expression level of immune suppressive factors of MDSCs, arginase-1 (Arg-1) and ROS, in purified MDSCS from tumor tissue in vivo. Expectedly, curcumin also inhibited the immunosuppressive function of isolated MDSCs from tumor tissue and spleen of tumor bearing mice in vitro. Moreover, curcumin decreased the level of IL-6 in the tumor tissue and serum from LLC-bearing mice. Taken together, curcumin indeed possesses anti-cancer effect and inhibits the accumulation and function of MDSCs. And curcumin reduces the level of IL-6 in tumor-bearing mice to impair the expansion and function of MDSCs. These results suggest that inhibition of MDSCs in tumor is requisite for controlling lung cancer. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:265 / 272
页数:8
相关论文
共 38 条
[1]   ESTABLISHMENT OF A CLONED LINE OF LEWIS LUNG-CARCINOMA CELLS ADAPTED TO CELL-CULTURE [J].
BERTRAM, JS ;
JANIK, P .
CANCER LETTERS, 1980, 11 (01) :63-73
[2]   Immune therapy of non-small cell lung cancer. The future [J].
Bobbio, Antonio ;
Alifano, Marco .
PHARMACOLOGICAL RESEARCH, 2015, 99 :217-222
[3]   Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression [J].
Bunt, Stephanie K. ;
Yang, Linglin ;
Sinha, Pratima ;
Clements, Virginia K. ;
Leips, Jeff ;
Ostrand-Rosenberg, Suzanne .
CANCER RESEARCH, 2007, 67 (20) :10019-10026
[4]   IL-6-stimulated CD11b+CD14+HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus [J].
Chen, Miao-Fen ;
Kuan, Feng-Che ;
Yen, Tzu-Chen ;
Lu, Ming-Shian ;
Lin, Paul-Yang ;
Chung, Yi-Hsiu ;
Chen, Wen-Cheng ;
Lee, Kuan-Der .
ONCOTARGET, 2014, 5 (18) :8716-8728
[5]   Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro [J].
Chiang, I-Tsang ;
Wang, Wei-Shu ;
Liu, Hsin-Chung ;
Yang, Su-Tso ;
Tang, Nou-Ying ;
Chung, Jing-Gung .
ONCOLOGY REPORTS, 2015, 34 (04) :1853-1874
[6]   Curcumin and cancer: barriers to obtaining a health claim [J].
Devassy, Jessay G. ;
Nwachukwu, Ifeanyi D. ;
Jones, Peter J. H. .
NUTRITION REVIEWS, 2015, 73 (03) :155-165
[7]   Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy [J].
Draghiciu, Oana ;
Lubbers, Joyce ;
Nijman, Hans W. ;
Daemen, Toos .
ONCOIMMUNOLOGY, 2015, 4 (01) :954829
[8]   Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway [J].
Fan, Zhigang ;
Duan, Xiaoyi ;
Cai, Hui ;
Wang, Li ;
Li, Min ;
Qu, Jingkun ;
Li, Wanjun ;
Wang, Yongheng ;
Wang, Jiansheng .
ONCOLOGY REPORTS, 2015, 34 (02) :691-698
[9]   Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway [J].
Fu, Zhongping ;
Chen, Xiao ;
Guan, Shengwen ;
Yan, Yanju ;
Lin, Huan ;
Hua, Zi-Chun .
ONCOTARGET, 2015, 6 (23) :19469-19482
[10]   Myeloid-derived suppressor cells as regulators of the immune system [J].
Gabrilovich, Dmitry I. ;
Nagaraj, Srinivas .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174