Matrine enhances the cytotoxic sensitivity of ABCG2high nasopharyngeal carcinoma cells to natural killer cells by inducing high expression of NKG2D receptor ligands

Objective To investigate the mechanism underlying the effects of matrine in enhancing the cytotoxic sensitivity of CNE2/DDP cells highly expressing ATP-binding cassette superfamily G member 2(ABCG2High) to allogenic natural killer(Allo-NK) cells.Methods ABCG2High CNE2/DDP cells and Allo-NK cells were isolated by magnetic activated cell sorting(MACS).Flow cytometry was used to evaluate the purity of the isolated cells and the expression of NKG2D ligands on the target cells before and after incubation with matrine.The cytotoxic sensitivity of the treated and non-treated ABCG2High CNE2/DDP cells to Allo-NK cells was measured by LDH releasing assay.Results The expression rate of ABCG2 was(91.40 ±2.32)% in ABCG2High CNE2/DDP cells.More than 90% of the isolated NK cells were identified to be CD3-CD16+CD56+ cells.The expression rates of MICA,MICB,ULBP1,ULBP2,and ULBP3 on the target cells incubated with matrine increased from(2.92±0.33)%,(4.27±0.33)%,(5.80±0.62)%,(11.10±3.15)%,and(7.75±1.14)% to(11.30± 0.89)%,(14.29±2.61)%,(12.56±1.06)%,(43.24±4.43)%,and(12.77±1.06)%,respectively.At the E:T ratio of 10:1 and 20:1,the cytotoxic sensitivity of ABCG2High cells to Allo-NK cells increased from(15.32 ±1.34)% and(27.26 ±6.81)% in un-treated cells to(28.53±1.37)% and(42.72±2.80)% in matrine-treated cells,respectively,showing significant differences in the cytotoxic sensitivity of the target cells in both groups produced by matrine treatment(F=29.05,P=0.000).Conclusion Matrine can up-regulate the expressions of NKG2D ligands(MICA/B and ULBP1-3) in ABCG2high nasopharyngeal carcinoma cells,which results in increased cytotoxic sensitivity of the cells to Allo-NK cells.