Bortezomib increases cytotoxic sensitivity of drug-resistant K562 /ADM cells to NK cells and its mechanisms
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Abstract:
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±128)% 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.
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Project supported by the Science and Technology Supporting Program of Gausu Province (No.0804NKCA115)