联合应用达沙替尼可增强吉非替尼对HCC827肺癌细胞的杀伤作用  

The combination of dasatinib and gefitinib enhances the killing effect of gefitinib on HCC827 lung cancer cells

作　　者：王志鸿[1,2] 李鲁[2] 邵壮[2] 解华杰 杨帆[2] 周乃康[1] 

机构地区：[1]中国人民解放军总医院,北京100853 [2]解放军306医院心胸外科,北京100101

出　　处：《细胞与分子免疫学杂志》2016年第5期595-599,共5页Chinese Journal of Cellular and Molecular Immunology

摘　　要：目的探讨达沙替尼(dasatinb)增强吉非替尼(gefitinib)对HCC827肺癌细胞杀伤作用的分子机制。方法单独(0、100、500、1000)nmol/L gefitinib及联合使用dasatinb(1000 nmol/L)处理HCC827细胞及gefitinib耐药株HCC827GR细胞,采用MTT法检测HCC827细胞、HCC827GR细胞增殖活力,采用分光光度法检测caspase 3活性,Western blot法检测各组细胞中Src、表皮生长因子受体(EGFR)蛋白磷酸化水平。结果 HCC827GR细胞中Src磷酸化水平显著增高,dasatinb显著抑制Src磷酸化水平,抑制细胞增殖并促进caspase 3表达,两种药物联合应用杀伤效果显著高于单纯gefitinib处理组。结论 Dasatinb与gefitinib联合应用可增强对Src家族表达的抑制,增强gefitinib对HCC827肺癌细胞的杀伤作用。Objective To investigate the molecular mechanism underlying that dasatinib enhances the killing effect of gefitinib on HCC827 lung cancer cells. Methods HCC827 cells and gefitinib-resistant HCC827GR cells were treated with 0, 100,500, 1000 nmol/L gefitinib alone or in combination with 1000 nmol/L dasatinib. The proliferation of HCC827 cells and HCC827GR cells was detected by MTT assay, the activity of caspase 3 was tested by spectrophotometry, and the protein phosphorylation levels of Src and epidermal growth factor receptor （EGFR） were examined by Westem blotting. Results Src phosphorylation level was obviously enhanced in HCC827GR cells. Dasatinib significantly inhibited Src phosphorylation, promoted the cell proliferation and the expression of caspase 3. The combination of gefitinib and dasatinib had the stronger killing effect than gefitinib alone did. Conclusion The combination of dasatinib and gefitinib can enhance the inhibition on the expression of Src protein and the killing effect of gefitinib on HCC827 lung cancer cells.

关 键 词：达沙替尼(dasatinb) 吉非替尼(gefitinib) 非小细胞肺癌 耐药 SRC激酶 

分 类 号：R965[医药卫生—药理学] Q279[医药卫生—药学]