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（0.001~10 μg/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IC50分别为0.085 3、0.098 2、0.043 5 μg/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% vs 29.33%、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 IC50 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.

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）