Abstract:
Objective This study aims to explore the effects of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) on the expression of natural killer group 2, member D receptor (NKG2D) ligands in human lung cancer A549 cells and on the cytotoxicity mediated by cytokine -induced killer (CIK) cells.
Methods The expression of NKG2D ligands (i.e., major histocompatibility complex class I chain-related molecules A or B (MICA, MICB), up-regulation of UL16-binding protein (ULBP)1, ULBP2, and ULBP3) on A549 cells were analyzed before and after treatment with erlotinib, phosphatidylinositol 3-kinase (PI3-K) selective inhibitors, mitogen-activated protein kinases (MAPK), and signal transducers and activators of transcription 3 (STAT3). The cytotoxicities of CIK cells against A549 cells before and after treatment with 10 μmol/L of erlotinib were detected by lactate dehydrogenase releasing assay at 10∶1, 20∶1, and 30∶1 effect-to-target cell ratios.
Results After treatment with 5 or 10 μmol/L of erlotinib, the MICB and ULBP1 expressions on A549 cells increased, whereas the MICA expression decreased (P<0.05). Minimal changes were observed on ULBP2 and ULBP3 (P>0.05). The inhibitors of EGFR downstream molecules, namely, MAPK inhibitors (SB203580) and STAT3 inhibitors (STAT21), had no effect on the expression of NKG2D ligands, whereas the PI3-K inhibitors (LY294002) decreased the MICA expression. The cytotoxicity of CIK cells against A549 cells treated with 10 μmol/L of erlotinib was significantly enhanced (P<0.05).
Conclusion Results indicate that the therapeutic efficacy of EGFR TKI in lung cancer may be mediated by increasing the susceptibility of cells to immune-cell-mediated cytotoxicity. Therefore, combination therapies with erlotinib and CIK cells may have clinical therapeutic significance for lung cancer patients.
下载: