Yao B Q, Jia Y, Guo J Q, Zhao Q, Sun H, Zhang J P
Department of Medical Oncology, Shanxi Dayi Hospital of Shanxi Academy of Medical Sciences, Taiyuan 030032, China.
Zhonghua Zhong Liu Za Zhi. 2017 Aug 23;39(8):573-578. doi: 10.3760/cma.j.issn.0253-3766.2017.08.003.
To explore the inhibitory effect of icotinib combined with cytokine induced killer (CIK) on various human lung adenocarcinoma cell lines in vitro. The inhibitory effect of icotinib alone or icotinib combined with CIK on HCC827 and A549 cells was detected by cell counting kit-8(CCK-8). The apoptosis was detected by flow cytometry via Annexin V/PI staining. The effect of icotinib on CIK phenotype was detected by flow cytometry. The inhibitory rates of HCC827 cells treated with 1.5, 3, 6, 12 μmol/L icotinib were (5.64±0.05)%, (8.62±0.45)%, (14.57±0.65)% and (18.52±0.91)%, respectively. The inhibitory rates of A549 cells were (1.64±0.48)%, (2.09±0.28)%, (3.69±0.45)%, (4.41±0.58)%, respectively. At the same concentration, the inhibitory rate of HCC827 cells with icotinib treatment was significantly higher than that of A549 cells (<0.05). When the effector/target ratio was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells co-cultured with CIK were (15.17±2.33)%, (42.59±7.18)%, (62.59±8.95)%, respectively, and the inhibitory rates of A549 were(16.99±2.81)%, (46.31±1.89)%, (58.24±4.23)%, respectively. The inhibitory rate of HCC827 cells co-cultured with CIK was not significantly different from that of A549 cells at the same effector/target ratio ((10∶1)=0.299, (20∶1)=0.318, (40∶1)=0.366). When the effector/target ratio of CIK combined with 6 μmol/L icotinib was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells were (37.07±3.50)%, (76.03±6.55)%, (80.34±10.69)%, respectively, and the inhibitory rates of A549 cells were(25.72±1.41)%, (52.76±3.82)%, (62.26±1.94)%, respectively. The inhibitory rates of 6 μmol/L icotinib combined with CIK were significantly higher than those of icotinib group and CIK group alone at the same effector/target ratio (<0.05), except for the effector/target ratio at 40︰1 on A549 cells (=0.089). Moreover, all of the combination index (CI) of combined group were <1 (<0.05). The apoptotic rates of HCC827 and A549 cells induced by icotinib combined with CIK were significantly higher than those of icotinib group and blank control group (<0.05), especially the proportion of late apoptotic or necrotic cells.Increasing effector/target ratio of CIK contributed to stronger inhibition(<0.05). The expressional rate of CIK phenotype with or without icotinib treatment was not significantly different from each other(>0.05). EGFR mutant lung adenocarcinoma cells are more sensitive to icotinib, while the EGFR mutation status has no effect on the killing effect of CIK cells. icotinib combined with CIK has a synergistic effect on the inhibition of tumor growth, and icotinib has no any impact on the phenotype of CIK cells.
探讨埃克替尼联合细胞因子诱导的杀伤细胞（CIK）对多种人肺腺癌细胞系的体外抑制作用。采用细胞计数试剂盒-8（CCK-8）检测埃克替尼单独或联合CIK对HCC827和A549细胞的抑制作用。通过Annexin V/PI染色利用流式细胞术检测细胞凋亡情况。采用流式细胞术检测埃克替尼对CIK表型的影响。1.5、3、6、12 μmol/L埃克替尼处理的HCC827细胞的抑制率分别为（5.64±0.05）%、（8.62±0.45）%、（14.57±0.65）%和（18.52±0.91）%。A549细胞的抑制率分别为（1.64±0.48）%、（2.09±0.28）%、（3.69±0.45）%、（4.41±0.58）%。在相同浓度下，埃克替尼处理的HCC827细胞的抑制率显著高于A549细胞（<0.05）。当效应细胞/靶细胞比例为10∶1、20∶1或40∶1时，与CIK共培养的HCC827细胞的抑制率分别为（15.17±2.33）%、（42.59±7.18）%、（62.59±8.95）%，A549细胞的抑制率分别为（16.99±2.81）%、（46.31±1.89）%、（58.24±4.23）%。在相同效应细胞/靶细胞比例下，与CIK共培养的HCC827细胞的抑制率与A549细胞的抑制率差异无统计学意义（（10∶1）=0.299，（20∶1）=0.318，（40∶1）=0.366）。当CIK与6 μmol/L埃克替尼联合的效应细胞/靶细胞比例为10∶1、20∶1或40∶1时，HCC827细胞的抑制率分别为（37.07±3.5）%、（76.03±6.55）%、（80.34±10.69）%，A549细胞的抑制率分别为（25.72±1.41）%、（52.76±3.82）%、（62.26±1.94）%。在相同效应细胞/靶细胞比例下，6 μmol/L埃克替尼联合CIK的抑制率显著高于埃克替尼组和CIK单独处理组（<0.05），A549细胞在效应细胞/靶细胞比例为40︰1时除外（=0.089）。此外，联合组的所有联合指数（CI）均<1（<0.05）。埃克替尼联合CIK诱导的HCC827和A549细胞的凋亡率显著高于埃克替尼组和空白对照组（<0.05），尤其是晚期凋亡或坏死细胞的比例。增加CIK的效应细胞/靶细胞比例导致更强的抑制作用（<0.05）。有无埃克替尼处理的CIK表型表达率差异无统计学意义（>0.05）。表皮生长因子受体（EGFR）突变的肺腺癌细胞对埃克替尼更敏感，而EGFR突变状态对CIK细胞的杀伤作用无影响。埃克替尼联合CIK对肿瘤生长的抑制具有协同作用，且埃克替尼对CIK细胞的表型无任何影响。
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