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作 者:孙非凡[1] 孙铭娟[2] 王梁华[2] 焦炳华[2]
机构地区:[1]第二军医大学研究生管理大队,上海200433 [2]第二军医大学基础部生物化学与分子生物学教研室,上海200433
出 处:《中国肿瘤生物治疗杂志》2011年第3期296-300,共5页Chinese Journal of Cancer Biotherapy
基 金:科技部"重大新药创制"科技重大专项(No.2009ZX09103-689);第二军医大学大学生创新能力培养研究课题资助项目(No.MS2009033)~~
摘 要:目的:观察吉西他滨(gemcitabine)联合TNF相关凋亡诱导配体(TNF-related apoptosis inducing ligand,TRAIL)对人肺癌细胞NCI-H460增殖和凋亡的影响。方法:MTT法检测NCI-H460细胞的增殖,流式细胞术检测NCI-H460细胞的凋亡。结果:吉西他滨和TRAIL单用或联用均可浓度(0.00110μg/ml)和时间(24、48、72 h)依赖性抑制NCI-H460细胞的增殖,两药联用比单用时抑制率更高,3组药物作用72 h时对肿瘤的抑制率分别为14.9%77.5%、23.4%74.8%、22.3%80.5%;作用72 h时两药单用和联用对细胞增殖抑制的IC50分别为0.085 3、0.098 2、0.043 5μg/ml。两药联用对NCI-H460细胞增殖的抑制效果还与用药顺序以及两药比例有关,吉西他滨作用24 h后再加TRAIL比TRAIL作用24 h后再加吉西他滨对NCI-H460的抑制效果更好,吉西他滨与TRAIL联用的比例为1∶0.3时对NCI-H460细胞增殖的抑制率最大。吉西他滨和TRAIL联用时NCI-H460细胞的凋亡率显著高于两药单用的凋亡率(49.04%vs29.33%、25.69%,P〈0.01)。结论:吉西他滨与TRAIL联用可协同抑制肺癌细胞NCI-H460的增殖、促进细胞凋亡。Objective:To study the effect of gemcitabine combined with TRAIL(TNF-related apoptosis inducing ligand) on proliferation and apoptosis of human lung cancer NCI-H460 cells.Methods: MTT assay was used to analyze the proliferation of NCI-H460 cells,and flow cytometry was used to examine the apoptosis of NCI-H460 cells.Results: Gemcitabine or TRAIL alone or in combination inhibited the proliferation of NCI-H460 cells in a time-(24,48,72 h) and concentration-dependent(0.001-10 μg/ml) manner.Gemcitabine combined with TRAIL had a stronger inhibitory effect than they were used alone,with the inhibitory ratios being 14.9%-77.5%,23.4%-74.8%,and 22.3%-80.5% after 72 h in combination,gemcitabine,and TRAIL groups,and the IC50 being 0.0853,0.0982,and 0.0435 μg/ml respectively.The inhibitory effect of gemcitabine combined with TRAIL on proliferation of NCI-H460 cells was related to the administration order and the ratio of gemcitabine and TRAIL;gemcitabine treatment for 24 h and then giving TRAIL had a stronger inhibitory effect than TRAIL treatment for 24 h and then giving gemcitabine;when the ratio of gemcitabine and TRAIL was 1:0.3,the combination showed the strongest inhibitory effect.The apoptosis rate of NCI-H460 cells in the combination treatment group was significantly higher than in the other two groups(49.04% vs 29.33%,25.69%,P〈0.01).Conclusion: Gemcitabine and TRAIL have synergistic effects in inhibiting proliferation and promoting apoptosis of lung cancer NCI-H460 cells.
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