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舒尼替尼体内诱导耐药鼻咽癌细胞表达NKG2DLs增强NK细胞的抑瘤作用
引用本文:黄宇贤,王 杨,李玉华,宋朝阳,陈土珍,周 璇,涂三芳,何颖芝,郭坤元.舒尼替尼体内诱导耐药鼻咽癌细胞表达NKG2DLs增强NK细胞的抑瘤作用[J].中国肿瘤生物治疗杂志,2010,17(3):262-267.
作者姓名:黄宇贤  王 杨  李玉华  宋朝阳  陈土珍  周 璇  涂三芳  何颖芝  郭坤元
作者单位:1. 南方医科大学,珠江医院,血液科,广东,广州,510282
2. 广东省人民医院,肺癌研究所,广东,广州,510080
基金项目:国家自然科学基金资助项目(No. 30973454);广东省自然科学基金重点项目(No. 9251051501000007)
摘    要:目的:探讨体内条件下舒尼替尼对耐药鼻咽癌CNE2/DDP细胞NKG2DLs(natural killer group 2 member D ligands)表达的诱导作用,及其对NK细胞抗肿瘤活性的影响。方法:建立ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞裸鼠皮下移植瘤模型,分如下8组:A、E组分别接种ABCG2high、ABCG2lowCNE2/DDP细胞,B、F组分别接种舒尼替尼处理的ABCG2high、ABCG2lowCNE2/DDP细胞,C、G组分别接种ABCG2high、ABCG2lowCNE2/DDP细胞后再输注NK细胞;D、H组接种舒尼替尼处理的ABCG2high、ABCG2lowCNE2/DDP细胞后再输注NK细胞。检测各组裸鼠成瘤时间、成瘤率、肿瘤体积和抑瘤率。免疫组织化学法检测移植瘤组织中NKG2DLs的表达。结果:A、B、C、D和E、F、G、H组肿瘤出现时间分别为(5.43±1.00)、(8.50±035)、(1110±1.25)、(13.56±1.23) d和 (9.00±1.00)、(12.30±0.78)、(14.50±0.50)、(17.25±0.77) d,其中舒尼替尼与NK细胞联合处理组(D 和H 组)成瘤时间最晚(P<0.01)。A、B、C、D和E、F、G、H组肿瘤质量分别为(2.63±089)、(1.00±003)、(065±0.08)、(0.21±0.27) g和(2.79±0.83)、(1.18±0.77)、(0.96±0.50)、(0.86±0.82) g,其中舒尼替尼与NK细胞联合处理组肿瘤质量最小(P<001);舒尼替尼与NK细胞联合处理的D组和H组的抑瘤率分别为92%和69%。舒尼替尼上调移植瘤组织中NKG2DLs的表达,且ABCG2highCNE2/DDP细胞移植瘤中的NKG2DLs表达率高于ABCG2lowCNE2/DDP细胞。结论:舒尼替尼可在体内诱导CNE2/DDP移植瘤组织表达NKG2DLs,增强NK细胞的抗肿瘤作用。

关 键 词:舒尼替尼  自然杀伤细胞  NKG2D配体  鼻咽肿瘤  裸鼠移植瘤
收稿时间:2009/12/12 0:00:00
修稿时间:2010/1/28 0:00:00

Sunitinib enhances inhibitory effect of NK cells against xenografts in nude mice by up regulating NKG2DLs expressions in multidrug resistant nasopharyngeal carcinoma cells
HUANG Yu-xian,WANG Yang,LI Yu-hu,SONG Chao-yang,CHEN Tu-zhen,ZHOU Xuan,TU San-fang,HE Ying-zhi and GUO Kun-yuan.Sunitinib enhances inhibitory effect of NK cells against xenografts in nude mice by up regulating NKG2DLs expressions in multidrug resistant nasopharyngeal carcinoma cells[J].Chinese Journal of Cancer Biotherapy,2010,17(3):262-267.
Authors:HUANG Yu-xian  WANG Yang  LI Yu-hu  SONG Chao-yang  CHEN Tu-zhen  ZHOU Xuan  TU San-fang  HE Ying-zhi and GUO Kun-yuan
Institution:Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Lung Cancer Institute, Guangdong General Hospital, Guangzhou 510080, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China;Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China
Abstract:Objective To investigate the effect of sunitinib on NKG2D ligands(NKG2DLs) expressions and its influences on anti-tumor effect of NK cells.Methods: ABCG2highCNE2/DDP-and ABCG2lowCNE2/DDP cell-implanted mouse tumor models were established and were divided into the following 8 groups.A,E: inoculated with ABCG2highCNE2/DDP or ABCG2low CNE2/DDP cells;B,F: inoculated with sunitinib-stimulated ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells;C,G: inoculated with ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells ...
Keywords:sunitinib  natural killer cell  natural killer group 2 member D ligand(NKG2DL)  nasopharyngeal neoplasmas  xenograft in nude mice  
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