EGFR靶向抑制剂ZD1839联合放疗对非小细胞肺癌细胞凋亡的影响及其机制研究  

Effect of EGFR-targeted Inhibitor ZD1839 Combined with Radiotherapy on Apoptosis of Non-small-cell Lung Cancer Cells and Its Mechanism

作　　者：林珊[1] 孟玲楠[1] 珊丹[1] 高纯子[1] 李孟阳[1] 韩波[1] LIN Shan;MENG Ling-nan;SHAN Dan;GAO Chun-zi;LI Meng-yang;HAN Bo(The Second Department of Oncology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China)

机构地区：[1]哈尔滨医科大学附属第一医院肿瘤二科,哈尔滨150001

出　　处：《解放军医药杂志》2019年第3期34-38,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：黑龙江省科学基金面上项目(H2016041)

摘　　要：目的研究表皮生长因子受体(EGFR)靶向抑制剂ZD1839联合放疗对非小细胞肺癌(NSCLC)细胞凋亡的影响及其机制。方法体外培养人NSCLC细胞株A549和HCC827,将2种细胞株均分为A组不作处理、B组给予ZD1839、C组给予放疗、D组给予ZD1839联合放疗,其中A549细胞株记为A1组、B1组、C1组、D1组,HCC827细胞株记为A2组、B2组、C2组、D2组。测定各组的细胞增殖抑制率、计算2 Gy照射剂量下细胞存活分数(SF2值)、检测细胞凋亡和细胞周期情况以及EGFR、p-EGFR及磷酸化蛋白激酶B(p-Akt)水平。结果 D1组细胞增殖抑制率高于B1组和C1组,SF2值低于C1组(P<0.05)。B1、C1和D1组G1/G0期比例和细胞凋亡率高于A1组,D1组高于B1和C1组(P<0.05)。B1、C1和D1组的S期和G2/M期比例以及EGFR、p-EGFR、p-Akt表达水平低于A1组,且D1组低于B1和C1组(P<0.05)。4组HCC827细胞上述观察指标比较差异均无统计学意义(P>0.05)。结论 EGFR靶向制剂ZD1839联合放疗可将NSCLC细胞阻滞于G1/G0期,增强放射线诱导细胞凋亡,可能与抑制EGFR、p-EGFR和p-Akt有关。Objective To study effect of epidermal growth factor receptor (EGFR) targeted inhibitor ZD1839 combined with radiotherapy on apoptosis of non-small cell lung cancer (NSCLC) cells and its mechanism. Methods Human NSCLC cell lines of A549 and HCC827 were cultured in vitro. The two cell lines were equally divided into group A without treatment, group B treated with ZD1839, group C treated with X-ray radiotherapy and group D treated with ZD1839 combined with X-ray radiotherapy. The A549 cell lines were recorded as subgroup A1, B1, C1 and D1, while HCC827 cell lines were recorded as subgroup A2, B2, C2 and D2. Cell proliferation inhibition rates were detected, and cell survival fraction (SF2) values at 2 Gy irradiation dose were calculated, and conditions of cell apoptosis and cell cycle were detected, and levels of EGFR, phosphorylated EGFR (p-EGFR) and phosphorylated protein kinase B (p-Akt) were detected in all subgroups. Results In subgroup D1, cell proliferation inhibition rate was higher than those in subgroup B1 and C1, while SF2 value was lower than that in subgroup C1 ( P <0.05). Ratios of G1/G0 phase and apoptotic rates in subgroup B1, C1 and D1 were higher than those in subgroup A1, and the values in subgroup D1 were higher than those in subgroup B1 and C1 ( P <0.05). Proportions of S phase and G2/M phase and EGFR, p-EGFR and p-Akt expressions in subgroup B1, C1 and D1 were lower than those in subgroup A1, and the values in subgroup D1 were lower than those in subgroup B1 and C1 ( P <0.05). There were no significant differences in the above indexes of HCC827 cells among four subgroups ( P >0.05). Conclusion EGFR targeted inhibitor ZD1839 combined with radiotherapy may block NSCLC cells in G1/G0 phase and enhance radiation-induced apoptosis, which may be related to inhibition of EGFR , p-EGFR and p-Akt.

关 键 词：癌 非小细胞肺 受体 表皮生长因子 ZD1839 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤]