Abstract:
Objective To investigate the mechanism on the effect s of improving cytotoxic sensitivity of ABCG2 High CNE2/ DDP cells to Allo2N K cells which exerted by bortezomib. Methods ABCG2 HighCNE2/DDP cells and Allo2N K cells were isolated by magnetic activated cell sorting (MACS) . Flow cytomet ry was used to evaluate the purity of isolated cells and the expression of N KG2D2ligands on target cells be2 fore and af ter incubation with bortezomib. Subsequently, the cytotoxic sensitivity of t reated and un2t reated ABCG2 High CNE2/ DDP cells to Allo2N K cells were measured by LDH releasing assay. Results The ex2 pressions of ABCG2 in ABCG2 High CNE2/ DDP cells were (91. 40 ±2. 32) %. More than 90 % of isolated N K cells showed tobe CD3 - CD16 + CD56 + cells which would definitely meet the needs of experiment s. The expressions of MICA、MICB、ULBP1 、ULBP2 、ULBP3 on target cells incubated with bortezomib have respectively increased f rom ( 2. 92 ±0. 33) %, ( 4. 27 ±0. 33) %, ( 5. 80 ±0. 62 ) %, ( 11. 10 ±3. 15 ) %, (7. 75 ±1. 14) % to (17. 52 ±2. 04) %、(12. 53 ±3. 68) %、(15. 24 ±2. 91) %、(62. 02 ±6. 85) %、(35. 69 ±3. 23) %. At the E∶T ratio of 10∶1 and 20∶1, the cytotoxic sensitivity of ABCG2 HighCNE2/ DDP cells to Allo2N K cells increased f rom (15. 32 ±13. 86) % and (27. 26 ±6. 81) % in un2t reated groups to (35. 06 ±5. 10) % and (52. 34 ±4. 78) % in bortezomib t reated groups. Data above showed that cytotoxic sensitivity of target cells in each group before and af ter bortezomib t reatment had significant differences ( F = 26. 03 P = 0. 000) . Conclusion Bortezomib can up2regulate expressions of N KG2D2ligands (MICA/ B、ULBP123 ) in ABCG2 High nasopharyngeal carcinoma cells, which resulted in higher cytotoxic sensitivity to Allo2N K cells.