奥沙利铂对人低分化鼻咽癌细胞系CNE2体外增殖的影响

Study of cell growth inhibition and apoptosis induced by oxaliplatin in human poor differentiation nasopharyngeal carcinoma cell line-CNE2

背景与目的:奥沙利铂是第三代铂类化合物,与顺铂相比其作用机制有一些重要区别,且毒性较低。鼻咽癌以低分化癌为多见,虽放射治疗是基本手段,但对复法或转移鼻咽癌、化疗仍是重要的手段,因此,本实验通过探讨奥沙利铂体外对人低分化鼻咽癌细胞CNE2的影响研究其在鼻咽癌治疗中的可能价值。方法:将浓度分别为0.03、0.16、0.8、4.0、20.0、100μg/m l的奥沙利铂与CNE2细胞作用24、36、48 h,用MTT法计算细胞生长抑制率,流式细胞仪检测细胞周期改变和凋亡率,透射电镜观察其形态学变化。结果:奥沙利铂能够抑制CNE2细胞的增殖,并且这种作用呈时间和剂量依赖性。100μg/m l奥沙利铂作用48 h,CNE2细胞生长抑制率达(95.6±0.7)%。流式细胞仪分析显示CNE2细胞呈G2/M期阻滞;奥沙利铂浓度为0、0.03、4.0、100μg/m l时CNE2细胞的凋亡率分别为(0.19±0.17)%、(0.37±0.09)%、(5.50±1.08)%、(9.43±0.09)%。20μg/m l药物作用24 h后电镜观察发现CNE2细胞皱缩,染色质聚集于核膜周围,固缩,碎裂成多块;并有凋亡小体形成。结论:奥沙利铂能够抑制人低分化鼻咽癌细胞系CNE2的增殖,能够诱导CNE2细胞G2/M期阻滞,较高浓度的奥沙利铂才可诱导CNE2细胞凋亡。

Background and purpose： Baekgrnunds and Objective： Oxaliplatin is a third-generation platinum compound, there are some distinet differeuees in mechanism between cisplatin and oxaliplatin, and oxaliplatin is less toxic Poorly differentiated cartionla is the most common histological type, fnr nasopharyngeal carcinoma, although radiotherapy is the basic therapeutic approach to nasopharyngeal carciuoma, chemotherapy is also important for recurrent and metastatic nasopharyngeal carcinoma, so in this work we analyzed the effects of oxaliplatin on nasopharyngeal carcinoma cell lines in vitro. Methods： CNE2 was incubated with oxaliplatin at various concentrations and times, cell growth inhibition was assessed by MTT-microcultnre tetrazolium assay, cell-cycle kinetics and apoptosis were analyzed by flow cytometry and microscopy transmission electron, Results： Growth of CNE2 cells was signiticantly inhibited in a dose-dependent and time-dependment fashion. The inhibition of cell growth inhibition was （95.6±0.7）% after incubation with 100 ug/ml oxaliplatin for 48 hours, the cell was arrested at G2/M and apoptosis was indueed, When CNE2 cells were treated with oxaliplatin at the coneentration of 0,0, 03,4, 0,100 μg/ml, the rates of CNE2 cell apoptosis were （0.19± 0.17） % ,（ 0.37±0.09） % ,（ 5.50±1.08）% ,（9.43±0.09）%, respectively, 24 hours after 20μg/ml the CNE2 cells were characterized by chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptosis body by transmission electron microscopy , Conclusions： Oxaliplatin suppresses life growth of CNE2 cells in vitro by causing cell-cycle arrest and cell apoptosis.