目的：探讨硼替佐米提高耐药K562/ADM细胞对NK细胞杀伤敏感性的可能机制。 方法： 流式细胞术和real-time PCR检测硼替佐米处理前后K562/ADM细胞表面MHC Ⅰ类链相关分子A（major histocompatibility complex classⅠchain-related molecule A，MICA）蛋白和mRNA的表达，LDH释放法检测硼替佐米处理前后K562/ADM细胞对NK细胞的杀伤敏感性。 结果： 硼替佐米处理后，K562/ADM细胞表面MICA蛋白表达率上升\[（17.03±4.94）% vs （23.77±5.26）%，P<0.05\]；处理后K562/ADM细胞MICA mRNA的表达水平是处理前的（2.03±0.33）倍。效靶比为10∶1、20∶1时，NK细胞对硼替佐米处理后的K562/ADM细胞的杀伤率上升\[（23.22±3.03）%、（30.30±0.74）% vs（33.69±1.28）%、（41.40±1.97）%，P<005\]。 结论： 硼替佐米提高耐药K562/ADM细胞对NK细胞杀伤的敏感性，其机制可能与硼替佐米上调K562/ADM细胞MICA表达有关。

Objective : To investigate the effects of bortezomib on the cytotoxic sensitivity of drug-resistant K562/ADM cells to natural killer (NK) cells and the underlying mechanisms. Methods: The expressions of MICA protein and mRNA on K562/ADM target cells before and after incubation with bortezomib were detected by flow cytometry and real-time PCR, respectively. The cytotoxic sensitivity of K562/ADM cells treated with or without bortezomib to NK cells was measured by LDH releasing assay. Results: The expression rates of MICA protein on K562/ADM cells incubated with bortezomib increased from (17.03±4.94)% to (23.77±5.26)% (P<0.05). The mRNA expression of MICA on K562/ADM cells treated with bortezomib increased (2.03±0.33) times. At the E∶T ratio of 10∶1 and 20∶1, the cytotoxic sensitivity of K562/ADM cells to NK cells increased from (23.22±3.03)% and (30.30±0.74)% in untreated cells to (33.69±128)% and (41.40±1.97)% in bortezomib-treated cells, respectively, showing significant differences (P<0.05). Conclusion: Bortezomib can up-regulate the MICA expression in K562/ADM cells and thus may enhance the cytotoxicity of NK cells against K562/ADM cells.

甘肃省科技支撑计划资助项目(No.0804NKCA115)