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Monographic Report
Molecular targeted agents induce NKG2DLs expressions in multidrug resistant nasopharyngeal carcinoma CNE2/DDP cells
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Abstract:
Objective:To investigate molecular targeted agentinduced expressions of natural killer group 2 member D ligands (NKG2D ligands, NKG2DLs) in multidrug resistant nasopharyngeal carcinoma cell line CNE2/DDP with high or low ATPbinding cassette superfamily G member 2 expression (ABCG2 highCNE2/DDP cells or ABCG2lowCNE2/DDP cells) and its effects on their cytotoxic sensitivities to NK cells. Methods: ABCG2highCNE2/DDP cells, ABCG2lowCNE2/DDP cells and NK cells were isolated by magnetic activated cell sorting. Purity of the isolated cells and expression rates of NKG2DLs on ABCG2highCNE2/DDP and ABCG2lowCNE2/DDP cells before and after treatment with different molecular targeted agents (bortezomib, sorafenib, sunitinib) were examined by flow cytometry (FCM). Cytotoxic sensitivities of ABCG2highCNE2/DDP and ABCG2 lowCNE2/DDP cells were measured by LDH releasing assay. Results: Expression rates of ABCG2 on ABCG2 highCNE2/DDP and ABCG2lowCNE2/DDP cells were (91.40±2.32)% and (1.70±024)%, respectively. More than 90% of the isolated NK cells were CD3-CD16+CD56+ cells. Expressions of 5 types of NKG2DLs (MICA, MICB, ULBP1, ULBP2 and ULBP3) on untreated ABCG2highCNE2/DDP and ABCG2lowCNE2/DDP cells were relatively low, but their expressions were significantly upregulated after treatment with different molecular targeted agents (bortezomib, sorafenib, sunitinib), with the highest NKG2DLs expressions found in the sunitinibtreated group cells. In addition, cytotoxic sensitivities of ABCG2highCNE2/DDP and ABCG2lowCNE2/DDP cells to NK cells were increased with the upregulated expressions of NKG2DLs. Conclusion: Different molecular targeted agents can upregulate NKG2DLs expressions in human multidrug resistant nasopharyngeal carcinoma cells, with sunitinib showing the highest induction ability. A linear correlation exists between NKG2DLs expressions and tumor cell cytotoxic sensitivities to NK cells.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30973454), and the Key Program of Natural Science Foundation of Guangdong Province (No. 9251051501000007)
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