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目的探讨表皮生长因子受体(EGFR)抑制剂吉非替尼联合环氧合酶-2(COX-2)抑制剂塞来昔布对肺腺癌A549细胞株凋亡和EGFR、COX-2表达的影响。方法A549细胞培养于RPMI-1640培养液中,实验分为正常对照组、吉非替尼5μmol/L组、塞来昔布25μmol/L组、吉非替尼5μmol/L联合塞来昔布25μmol/L组。药物干预细胞48 h后,采用四甲基偶氮唑盐(MTT)比色法测定细胞抑制率、流式细胞术和Hoechst33258染色法检测细胞凋亡和药物作用周期、免疫荧光检测EGFR和COX-2蛋白的表达情况。结果吉非替尼和塞来昔布对A549细胞增殖有明显的抑制作用,呈剂量依赖性,两制剂联合作用时抑制作用更强(P<0.01)。吉非替尼和塞来昔布均可诱导细胞凋亡,联合作用后细胞凋亡率更高(P<0.01);联合用药与单独用药相比,可使细胞发生明显的G1期阻滞(P<0.01),进一步下调了EGFR和COX-2蛋白的表达(P<0.05)。结论吉非替尼与塞来昔布联合应用具有协同作用,可进一步抑制细胞的生长。
Objective To investigate the apoptosis and the expression of EGFR and COX-2 in lung adenocarcinoma A549 cell line with epidermal growth factor receptor (EGFR) inhibitor gefitinib combined with cyclooxygenase-2 (COX-2) inhibitor celecoxib Impact. Methods A549 cells were cultured in RPMI-1640 culture medium and divided into 5 groups: normal control group, gefitinib 5μmol / L group, celecoxib 25μmol / L group, gefitinib 5μmol / L combined with celecoxib 25μmol / / L group. After 48 h, the cell inhibition rate was determined by MTT colorimetric assay. The apoptosis and drug action cycle were detected by flow cytometry and Hoechst33258 staining. The expression of EGFR and COX- 2 protein expression. Results Gefitinib and celecoxib significantly inhibited the proliferation of A549 cells in a dose-dependent manner. The combination of the two agents significantly inhibited the proliferation of A549 cells (P <0.01). Gefitinib and celecoxib could induce apoptosis, and the apoptotic rate was higher after the combined treatment (P <0.01). Compared with the drug alone, the combination of gefitinib and celecoxib could induce G1 arrest P <0.01), further down-regulated EGFR and COX-2 protein expression (P <0.05). Conclusion The combination of gefitinib and celecoxib has a synergistic effect to further inhibit cell growth.