| Dong Zhuo,Gong Xinkou,Lyu Yahui,Yu Duo,Guo Xinyuan,Liu Yiting,Shao Lihong,Wei Wei,Gao Hui,Jin Shunzi.The mechanisms of tumor microenvironment in neuropilin 1-induced radiation resistance[J].Chinese Journal of Radiological Medicine and Protection,2017,37(2):81-87 |
| The mechanisms of tumor microenvironment in neuropilin 1-induced radiation resistance |
| Received:October 14, 2016 |
| DOI：10.3760/cma.j.issn.0254-5098.2017.02.001 |
| KeyWords:Tumor microenvironment Neuropilin 1(NRP1) Radioresistance Three dimensional culture |
| FundProject:国家自然科学基金（81573085，81371890） |
| Author Name | Affiliation | E-mail | | Dong Zhuo | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Gong Xinkou | Department of Radiology, The Second Hospital of Jilin University, Changchun 130041, China | | | Lyu Yahui | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Yu Duo | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Guo Xinyuan | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Liu Yiting | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Shao Lihong | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Wei Wei | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Gao Hui | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | | | Jin Shunzi | College of Public Medicine, Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun 130021, China | jinsz@jlu.edu.cn |
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| Abstract:: |
| Objective To study the effect of neuropilin 1(NRP1) on the inflammatory and migration of tumor microenvironment and explore the role of inflammatory cytokines and chemokines in NRP1-induced radiation resistance in tumor microenvironment of lung cancer cells.Methods NRP1LowA549 and A549-RR cell models were constructed and the expression levels of NRP1 in these models were identified. The three-dimensional co-culture models of A549+Jurkat, NRP1LowA549+Jurkat, A549-RR+Jurkat and A549+HLF-1, NRP1LowA549+HLF-1, A549-RR+HLF-1, and control group and irradiated group were established. After co-culturing 2 days, the cells were irradiated with 10 Gy X-rays. After 24 h, the culture medium supernatant of each model was collected and the expressions of related factors were detected by flow cytometry using cytometric bead array (CBA). Results The expression of NRP1 was inhibited in NRP1LowA549 cells but increased significantly in A549-RR cells. In the inflammatory microenvironment, the expressions of IL-12p70 and TNF in A549-RR+Jurkat group were significantly lower than those in A549+Jurkat group (t=3.88, 5.34, P<0.05). The expressions of IL-6 and IL-8 in A549-RR+Jurkat group were higher than those in A549+Jurkat group (t=38.30, 30.02, P<0.05), but decreased significantly after irradiation (t=14.39, 9.78, P<0.05). The expressions of IL-1β and IL-10 decreased in all groups after irradiation compared with the control group (t=2.80~11.22, P<0.05). Compared with A549+HLF-1 group, the expressions of RANTES and MCP-1 in NRP1LowA549+ HLF-1 group were significantly higher than those in A549+HLF-1 group (t=6.07, 4.04, P<0.05) and A549-RR+HLF-1 group (t=15.50, 14.62, P<0.05). After irradiation, RANTES and MCP-1 were decreased in all groups (t=2.23, 8.45, 16.68,P<0.05) in comparison with the control group. In contrast, the expression levels of IP-10 and CXCL8 (IL-8) were lower in A549+HLF-1 group than those in NRP1LowA549+HLF-1 group (t=31.86, 29.79, 6.62, 3.85, P<0.05). Conclusions NRP1 has significant effects on the expression of inflammatory cytokines and chemokines in inflammatory and migrating microenvironment of lung cancer, and these factors play an important role in the regulation of radiation resistance of lung cancer cells. |
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