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Sunitinib enhances inhibitory effect of NK cells against xenografts in nude mice by upregulating NKG2DLs expressions in multidrug resistant nasopharyngeal carcinoma cells
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Abstract:
Objective:To investigate the effect of sunitinib on NKG2D ligands (NKG2DLs) expressions and its influences on antitumor effect of NK cells. Methods: ABCG2highCNE2/DDP and ABCG2lowCNE2/DDP cellimplanted 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 sunitinibstimulated ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells; C, G: inoculated with ABCG2highCNE2/DDP cells or ABCG2lowCNE2/DDP cells and NK cells;and D, H: inoculated with sunitinibstimulated ABCG2highCNE2/DDP cells or ABCG2lowCNE2/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), (900±100), (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), (279±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 upregulated NKG2DLs expressions in implanted tumor tissues, with those in ABCG2highCNE2/DDP cells higher than those in ABCG2lowCNE2/DDP cells. Conclusion: unitinib can upregulate NKG2DLs expressions in CNE2/DDP cellimplanted tumor tissues in vivo and enhance antitumor effect of NK cells.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30973454), and the Key Program of Natural Science Foundation of Guangdong Province (No. 9251051501000007)
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