论文部分内容阅读
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ABCG2highCNE2/DDP和ABCG2lowCNE2/DDP细胞裸鼠皮下移植瘤模型,分如下8组:A、E组分别接种ABCG2high、ABCG2lowCNE2/DDP细胞,B、F组分别接种舒尼替尼处理的ABCG2high、ABCG2lowCNE2/DDP细胞,C、G组分别接种ABCG2high、ABCG2lowCNE2/DDP细胞后再输注NK细胞;D、H组接种舒尼替尼处理的ABCG2high、ABCG2lowCNE2/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ABCG2highCNE2/DDP细胞移植瘤中的NKG2DLs表达率高于ABCG2lowCNE2/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。
AIM: To investigate the induction of sunitinib on the expression of NKG2DLs (natural killer group 2 member D ligands) in nasopharyngeal carcinoma CNE2 / DDP cells in vivo and its effect on the antitumor activity of NK cells. METHODS: The subcutaneous xenograft models of ABCG2highCNE2 / DDP and ABCG2lowCNE2 / DDP were established in nude mice. The following groups were divided into 8 groups: group A and group E were inoculated with ABCG2high and ABCG2lowCNE2 / DDP cells, respectively. Groups B and F were treated with sunitinib-treated ABCG2high, The ABCG2high and ABCG2lowCNE2 / DDP cells were inoculated with ABCG2high and ABCG2lowCNE2 / DDP cells respectively, while those in ABCG2lowCNE2 / DDP, C and G groups were inoculated with NK cells. The D and H groups were inoculated with sunitinib-treated ABCG2high and ABCG2lowCNE2 / DDP cells. Tumor formation time, tumor formation rate, tumor volume and tumor inhibition rate were detected in each group. Immunohistochemistry was used to detect the expression of NKG2DLs in xenografts. Results: The tumor appearance time was (5.43 ± 1.00), (8.50 ± 0.35), (11.10 ± 1.25), (13.56 ± 1.23) d and (9.00) in group A, B, C, D and E, ± 0.78), (14.50 ± 0.50) and (17.25 ± 0.77) d, respectively, and the combination of sunitinib and NK cells had the latest tumor formation time (P <0.01) . The tumor mass in groups A, B, C, D and E, F, G and H were (2.63 ± 0.89), (1.00 ± 0.03), (0.65 ± 0.08), (0.21 ± 0.27) g and (2.79 ± 0.83) , (1.18 ± 0.77), (0.96 ± 0.50) and (0.86 ± 0.82) g, respectively, and the combination of sunitinib and NK cells had the lowest tumor mass (P <0.01) The inhibitory rates of tumors in group D and group H were 92% and 69%, respectively. Sunitinib upregulated the expression of NKG2DLs in xenografted tumor tissues, and the expression of NKG2DLs in ABCG2highCNE2 / DDP xenografts was higher than that in ABCG2lowCNE2 / DDP cells. Conclusion: Sunitinib can induce NKG2DLs expression in CNE2 / DDP xenografts in vivo and enhance the anti-tumor effect of NK cells.