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。

Objective:To investigate the effect of sunitinib on NKG2D ligands (NKG2DLs) expressions and its influences on antitumor effect of NK cells. Methods: ABCG2highCNE2/DDP and ABCG2lowCNE2/DDP cellimplanted mouse tumor models were established and were divided into the following 8 groups. A, E: inoculated with ABCG2highCNE2/DDP or ABCG2low CNE2/DDP cells; B, F: inoculated with sunitinibstimulated ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells; C, G: inoculated with ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells and NK cells;and D, H: inoculated with sunitinibstimulated ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells and NK cells.Tumor formation times and rates, tumor volumes, and tumor inhibitory rates were observed in different groups. NKG2DLs expressions in implanted tumor tissues were examined by immunohistochemistry assay. Results: Tumor formation times in A, B,C, D, E, F, G, and H groups were (5.43±1.00), (8.50±0.35), (11.10±1.25), (13.56±1.23), (900±100), (12.30±0.78),(14.50±0.50), and (17.25±0.77) d, respectively, with those in sunitinib and NK cell combination groups (D and H groups) being the longest ones (P<0.01). Tumor masses in A, B, C, D, E, F, G, and H groups were (2.63±0.89), (1.00±0.03), (0.65±0.08), (0.21±0.27), (279±0.83), (1.18±0.77), (0.96±0.50), and (0.86±0.82) g, respectively, with those in sunitinib and NK cell combination groups (D and H groups) being the lightest ones (P<0.01); the tumor inhibitory rates in sunitinib and NK cell combination groups (D and H groups) were 62% and 69%. Sunitinib upregulated NKG2DLs expressions in implanted tumor tissues, with those in ABCG2highCNE2/DDP cells higher than those in ABCG2lowCNE2/DDP cells. Conclusion: unitinib can upregulate NKG2DLs expressions in CNE2/DDP cellimplanted tumor tissues in vivo and enhance antitumor effect of NK cells.

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）