目的：观察地塞米松耐药的人B细胞淋巴瘤细胞系对NK细胞杀伤敏感性的变化，并探讨其作用机制。方法：20 μg/ml地塞米松（dexamethasone，DXM）诱导B细胞淋巴瘤细胞系SU-DHL-4（简称SU细胞）发生耐药，建立多药耐药细胞系SU/DXM。流式细胞术分选健康人外周血NK细胞，流式细胞术检测效靶比20∶1时，NK细胞对SU和SU/DXM细胞的杀伤效应。实时定量PCR检测SU和SU/DXM细胞表面NK细胞活化性受体（soluble NK group 2 member D，NKG2D）配体基因\[可溶性MHCⅠ类分子相关A/B（MHC class Ⅰ chain-related molecules A/B， MICA/B）及人UL16结合蛋白（UL16 binding protein，ULBP）1、2、3\]的表达。结果：成功建立多药耐药细胞系SU/DXM。与SU细胞相比，SU/DXM细胞对NK细胞杀伤的敏感性明显下降\[SU细胞为（11.38±3.51）%，SU/DXM细胞为（3.57±4.22）%，P<0.05\]，细胞表面NKG2D配体基因MICA、MICB、ULBP2 mRNA表达量降低（SU细胞分别为1.014±0.121、1.009±0.092、0.993±0.108，SU/DXM细胞分别为0.017±0.006、0.682±0.063、0.773±0.066，P<0.05或P<0.01）。结论：地塞米松能诱导B细胞淋巴瘤SU细胞发生多药耐药，多药耐药SU/DXM细胞能够抵抗NK细胞的杀伤，其机制可能与NKG2D配体基因表达量下降有关

Objective: To observe the change of cytotoxicity of NK cells on dexamethasone-resistant B-cell lymphoma cells, and study its mechanism. Methods: 20 μg/ml dexamethasone (DXM) was added to induce DXM-resistance B lymphoma SU-DHL-4 cells (SU cells). The multidrug resistance of SU cells was named SU-DXM cells. NK cells, sorted by flow cytometry was chosen as an effector, and the cytotoxicity of NK cells on SU and SU/DXM cells was analyzed through flow cytometry at E∶T was 20∶1. Real-time PCR was used to detect the gene expression of MHC class Ⅰ chain-related molecules A/B (MICA/B), UL16 binding protein (ULBP)1, ULBP2 and ULBP3 in both SU and SU/DXM cells. Results: After DXM treatment, the SU/DXM cells were established as a multi-drug-resistant cell line. Compared to SU cells, the cytotoyxicity sensitivity of NK cells on SU/DXM cells was obviously down-regulated (\[3.57±4.22\]% vs \[1138±3.51\]%, P<0.05), and the expressions of NKG2D ligand genes MICA, MICB and ULBP2 were statistically lower in SU/DXM cells (MICA: 0.017±0.006, MICB: 0.682±0.063, and ULBP: 20.773±0.066) than those in SU cells (MICA: 1.014±0.121, MICB: 1.009±0.092, and ULBP2: 0.993±0.108, P<0.05, P<0.01). Conclusion: Devamethasone has the ability to induce SU cells to multi-drug-resistant cells, SU/DXM cells, which resist the cytotoxicity mediated by NK cells, and the low gene expression of NKG2D ligands could be one important cause.

河南省科技厅科研项目(No.0611042000)