Synergistic lethal effects of cetuximab combined with chemotherapy and/or radiotherapy in laryngeal squamous carcinoma cells
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摘要: 目的:观察西妥昔单抗诱导人喉鳞状细胞癌细胞株Hep-2凋亡的敏感性,并探讨西妥昔单抗与顺铂、放射线联合应用对Hep-2细胞的杀伤效应及机制。方法:采用CCK-8试剂盒分别检测西妥昔单抗、顺铂、放射线对Hep-2生长抑制率,流式细胞仪检测不同干预方案对Hep-2凋亡率及细胞周期分布情况。结果:不同浓度西妥昔单抗对Hep-2细胞均有抑制作用,并在一定浓度范围内呈时间-剂量依赖性,24 h半数抑制浓度为1036.84 μg/ml;顺铂,放射线分别与西妥昔单抗联合应用时,Hep-2凋亡率显著高于顺铂、放射线单独或联合应用(P<0.01),并产生G0/G1期阻滞。结论:Hep-2细胞对西妥昔单抗诱导的细胞凋亡敏感,顺铂和(或)放射线与西妥昔单抗联用对Hep-2细胞的增殖具有协同抑制效应;显著的凋亡诱导作用和对Hep-2细胞周期的影响为其机制之一,为临床喉鳞状细胞癌靶向EGFR并联合放化疗方案提供了理论依据。Abstract: Objective: To determine the sensitivity of cetuximab induced apoptosis in laryngeal squamous carcinoma cells Hep-2,and to evaluate the synergistic killing effects and regulation mechanism of cetuximab alone or cetuximab in combination with chemotherapeutic agents(cisplatin) or radiation means on Hep-2 cells.Method: To investigate the cytotoxicities of cetuximab, cisplatin and radiation, cell counting kit-8(CCK-8) assay was used for the detection of cell growth inhibition ratio, and fluorescence activated cell sorterFACS for the apoptotic rate and cell cycle distribution.Result: Cetuximab had inhibitive effect on Hep-2 cells within a certain range of concentration in a time- and dose-dependence manner. The inhibition concentration 50%(IC50) of cetuximab on Hep-2 cells for 24 h was 1 036.84 μg/ml. For application of cisplatin and radiation, the apoptotic rate of Hep-2 cell was higher by combinining with cetuximab than their single or combined administration. Moreover, the cell cycle arrested at G0/G1 phase.Conclusion: Laryngeal cancer Hep-2 cells was sensitive to the cetuximab induced apoptosis. Cetuximab combined with cisplatin and/or radiation can increase the antiproliferative effects on Hep-2 cells. These findings suggest the synergistic combination of cetuximab and cytotoxic agents was sequence depended.
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Key words:
- laryngeal neoplasms /
- cetuximab /
- combined radiation and chemotherapy /
- apoptosis /
- synergism
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