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[1]张宏健,牛秀珑,段红洁,等.IL-17A对卵巢癌顺铂耐药的影响及其影响机制的研究[J].天津医科大学学报,2017,23(03):199-202.
　ZHANG Hong-jian,NIU Xiu-long,DUAN Hong-jie,et al.Study of the effects and underlying mechanisms of IL-17A on the cisplatin-based resistance of ovarian cancer[J].Journal of Tianjin Medical University,2017,23(03):199-202.
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IL-17A对卵巢癌顺铂耐药的影响及其影响机制的研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
23卷
期数:
2017年03期
页码:
199-202
栏目:
基础医学
出版日期:
2017-05-18

文章信息/Info

Title:
Study of the effects and underlying mechanisms of IL-17A on the cisplatin-based resistance of ovarian cancer
文章编号:
1006-8147(2017)03-0199-04
作者:
张宏健1; 牛秀珑2; 段红洁3; 李宏钊1; 刘文星1; 徐灵灵1; 邓为民1
( 1.天津医科大学免疫学系，天津市细胞与分子免疫学重点实验室，国家教育部免疫微环境与疾病重点实验室，天津300070；2.中国人民武装警察部队后勤学院附属医院感染性疾病科，天津300162；3.天津医科大学总医院输血科，天津300052)
Author(s):
ZHANG Hong-jian1;  NIU Xiu-long2;  DUAN Hong-jie3;  LI Hong-zhao1;  LIU Wen-xing1;  XU Ling-ling1;  DENG Wei-min1

(1.Department of Immunology ，Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology,? Tianjin 300070, China; 2.Department of Infectious Diseases, Hospital Affiliated to Logistics College of Chinese People’s Armed Police Forces, Tianjin 300162, China; 3. Department of Orthopedics, General Hospital, Tianjin Medical University，Tianjin 300052, China)

关键词:
IL-17A' target="_blank" rel="external">">IL-17A; DDP; 耐药; 卵巢癌
Keywords:
IL-17A;  cisplatin;  drug-resistance;  ovarian cancer
分类号:
R737.31
DOI:
-
文献标志码:
A
摘要:
?目的： 探究IL-17A 对卵巢癌（OVCA）顺铂(DDP)耐药的影响及其可能的作用机制。方法：应用MTT 法检测IL-17A（0.1、1、10、100 ng/mL，处理12、24、48、72 h）对A2780（顺铂敏感卵巢癌细胞株）和OVCAR3（顺铂耐药卵巢癌细胞株）增殖的影响；应用MTT 法检测IL-17A（1 ng/mL，处理 24 h）对A2780 和OVCAR3 细胞DDP 耐药的影响，并以rhIL-17RA 中和抗体（IL-17RAmAb）和Gli1 抑制剂Gant61 进行相应的阻断实验；应用Western blotting 法检测IL-17A 处理A2780 和OVCAR3细胞后，细胞中耐药相关分子ABCG2、MDR1 和Hedgehog（Hh）信号通路核转录因子Gli1 的蛋白表达，并分别以IL-17RAmAb 和Gant61 进行相应的阻断实验。结果： IL-17A 对A2780 和OVCAR3 的细胞增殖无显著性影响，但可显著增加DDP 降低的A2780 和OVCAR3 细胞活性（P<0.05），分别以IL-17RA mAb 和Gant61 进行阻断实验均可消除由IL-17A 加剧的A2780 和OVCAR3 细胞DDP 的耐药性；IL-17A 可上调A2780

和OVCAR3 细胞耐药相关分子ABCG2，MDR1 和Gli1 的蛋白表达并且分别以IL-17RAmAb 和Gant61 进行阻断实验均可抑制IL-17A 引起的A2780 和OVCAR3 细胞中ABCG2，MDR1 和Gli1 蛋白表达。结论： IL-17A可作用于IL-17RA并激活Gli1介导的Hh信号通路，进而促进耐药相关分子ABCG2和MDR1表达，从而加剧以DDP为基础的OVCA化疗耐药性。

Abstract:
Objective ：To study the effects and underlying mechanisms of IL-17A on the cisplatin-based resistance of ovarian cancer. Methods： MTT assay was used to detect the effect of IL-17A on cell growth, A2780 and OVCAR3 cells were treated with 0, 0.1, 1, 10 or 100 ng/mL IL-17A for 12, 24, 48 or 72 h. MTT assay was applied to detect the effect of viability of IL-17A (1ng/mL, 24 h) on A2780 and OVCAR3 cells treated with DDP (A2780, 10μmol/L; OVCAR3, 100μmol/L), and the neutralizing monoclonal antibody against IL-17A receptor (IL-17RA mAb) and the widely used chemical inhibitor for Gli1 (Gant61) were used to do the blocking test respectively. Western blotting assay was used carried out to detect the protein levels of ABCG2, MDR1 and Gli1 on IL-17A treated A2780 and OVCAR3 cells, and then neutralizing IL-17RA mAb and Gant61 were obtained to do the blocking test respectively. Results：IL-17A alone had no effect on the viability of A2780 and OVCAR3 cells, but it could increase the viability of A2780 and OVCAR3 cells with DDP treatment(P<0.05). Furthermore, neutralizing IL-17RA mAb and Gant 61 could respectively block the above effect of IL-17A on DDP-sensitivity significantly. IL-17A could increase the expressions of ABCG2, MDR1 and Gli1 in A2780 and OVCAR3 cells. Furthermore, neutralizing IL-17RA mAb and Gant 61 could respectively block the enhanced effects of IL-17A on ABCG2, MDR1 and Gli1 levels in A2780 and OVCAR3 cells. Conclusion：IL-17A can exacerbate cisplatin-based resistance of ovarian cancer cells via up-regulating the expression of ABCG2 and MDR1, partly through IL-17RA-Gli1-mediated Hh signal pathway, which may provide a novel strategy to improve the chemo-resistance of OVCA.

参考文献/References:

[1] Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling[J]. Cytokine, 2013, 64(2): 477
[2] Monteleone I, Pallone F, Monteleone G. Th17-related cytokines: new players in the control of chronic intestinal inflammation[J]. BMC Medicine, 2011, 9(1): 1
[3] Normanton M, Marti L C. Current data on IL-17 and Th17 cells and implications for graft versus host disease[J]. Einstein (Sao Paulo), 2013, 11(2): 237
[4] Liu W X, Li Z J, Niu X L, et al. The Role of T helper 17 cells and other IL-17-producing cells in bone resorption and remodeling[J]. Intern Rev Immunol, 2015, 34(4): 332
[5] Yang B, Kang H, Fung A, et al. The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis[J]. Mediators Inflamm ?，2014，2014:623759
[6] Xiang T, Long H, He L, et al. Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133&plus; cancer stem-like cells in ovarian cancer[J]. Oncogene, 2015, 34(2): 165
[7] Gottesman M M. Mechanisms of cancer drug resistance[J]. Annual Rev Med, 2002, 53(1): 615
[8] Peeper D S. Cancer drug resistance: Old concept, novel solutions required[J]. Mol Oncol, 2014, 8(6): 1064
[9] Droeser R A, Mechera R, D?ster S, et al. MPO density in primary cancer biopsies of ovarian carcinoma enhances the indicative value of IL-17 for chemosensitivity[J]. BMC Cancer, 2016, 16(1): 639
[10] Prabhala R H, Pelluru D, Fulciniti M, et al. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma[J]. Blood, 2010, 115(26): 5385
[11] Tartour E, Fossiez F, Joyeux I, et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice[J]. Cancer Res, 1999, 59(15): 3698
[12] Tonigold M, Rossmann A, Meinold M, et al. A cisplatin-resistant head and neck cancer cell line with cytoplasmic p53mut exhibits ATP-binding cassette transporter upregulation and high glutathione levels[J]. J Cancer Res Clin Oncol, 2014, 140(10): 1689
[13] Chen J, Wang J, Zhang Y, et al. Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture[J]. J Biosc Bioengineering, 2014, 118(2): 214
[14] Kruh G D. Introduction to resistance to anticancer agents[J]. Oncogene, 2003, 22(47): 7262
[15] Chen Y, Bieber M M, Teng N N H. Hedgehog signaling regulates drug sensitivity by targeting ABC transporters ABCB1 and ABCG2 in epithelial ovarian cancer[J]. Mol Carcinog, 2014, 53(8): 625

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备注/Memo

备注/Memo:

基金项目 天津市自然科学基金资助项目( 15JCYBJC26000)

作者简介 张宏健( 1990-) ，男，硕士在读，研究方向：肿瘤免疫；

通信作者 ：邓为民，E-mail: dengweimin@tijmu.edu.cn。

更新日期/Last Update: 2017-05-18