[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 (ABCG(2)(High)) to allogenic natural killer (Allo-NK) cells.


METHODS
ABCG(2)(High) 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 ABCG(2)(High) 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 ABCG(2)(High) 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 ABCG(2)(High) 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).


CONCLUSIONS
Matrine can up-regulate the expressions of NKG2D ligands (MICA/B and ULBP1-3) in ABCG(2)(High) nasopharyngeal carcinoma cells, which results in increased cytotoxic sensitivity of the cells to Allo-NK cells.
Huang
Yu-Xian
YX
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. hyx6610@163.com
Wang
Yang
Y
Sun
Ming
M
Zhou
Xue-Yun
XY
Deng
Lan
L
Guo
Kun-Yuan
KY
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism*; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D000093842:Matrines
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000470:Alkaloids; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; D011807:Quinolizines; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human; D000093842:Matrines