重组变构人肿瘤坏死因子相关凋亡诱导配体与吉西他滨联合对人非小细胞肺癌细胞株NCI-H460的体内外抑制作用

Inhibitory effects of a combination of rmhTRAIL and gemcitabine on human non-small cell lung cancer cell line NCI-H460 cells in vitro and in vivo

目的观察重组变构人肿瘤坏死因子相关凋亡诱导配体（rmhTRAIL）与吉西他滨（GEM）联合应用对人非小细胞肺癌细胞株NCI-H460在体内外的抑制作用。方法采用二苯基溴化四氮唑蓝（MTT）法，检测系列浓度的rmhTRAIL和GEM单独或联合应用时对人肺癌NCI-H460细胞生长的抑制作用。将NCI-H460细胞裸鼠移植瘤模型分为6组：对照组（腹腔注射生理盐水）、rmhTRAIL组、GEM组、rmhTRAIL＋GEM组、GEM＋顺铂（DDP）组和rmhTRAIL＋GEM＋DDP组，分别给药。每3～4d测量1次裸鼠移植瘤大小，用药后21d，处死裸鼠，剥取肿瘤称重。结果rmhTRAIL和GEM单独或联合应用时对NCI-H460细胞的生长抑制作用呈剂量依赖性，且系列浓度的rmhTRAIL和GEM的联合具有协同抑制作用。rmhTRAIL组、rmhTRML＋GEM组、GEM＋DDP组和rmhTRAIL＋GEM＋DDP组的相对肿瘤体积分别为4．75±3．04、2．53±1．25、4．52±2．87和1．69±0．97，均显著低于对照组（8．82±5．62，均P〈0．05）；肿瘤重量分别为（2．23±0．29）g、（1．12±0．77）g、（2．51±0．87）g和（0．60±0．18）g，均显著低于对照组[（4．71±0．97）g，均P〈0．01]。rmhTRAIL＋GEM组的相对肿瘤体积和肿瘤重量均显著低于rmhTRAIL组和GEM组（P〈0．05和P〈0．01）。rmhTRAIL＋GEM＋DDP组的相对肿瘤体积和肿瘤重量均显著低于rmhTRAIL组和GEM＋DDP组（P〈0．05和P〈0．01）。结论在体内外实验中，rmhTRAIL与吉西他滨联合对人肺癌细胞株NCI-H460的生长均显示出协同抑制作用。

Objective To evaluate the inhibitory effects of recombinant mutant tumor necrosis factor-related apoptosis-indueing ligand （rmhTRAIL） combined with chemotherapeutic agent gemcitabine （GEM） on human lung cancer cell line NCI-H460 cells in vitro and in vivo. Methods MTT was used to evaluate the cytotoxic effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI- H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor-bearing nude mice were randomly divided into 6 groups （n = 6） ： negative control group （to be injected intraperitoneally with normal saline）; rmhTRAIL group; GEM group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP group. The tumor size was measured every 3-4 days. Twenty one days after the administration of different drugs the miee were killed and the tumors were taken out and weighed. Results The growth inhibition of NCI-H460 cells was dose-dependent after exposure to rmhTRAIL, GEM alone or together. The combination of rmhTRAIL and GEM showed a synergistic inhibitory effect at different concentrations. The relative tumor volume of rmhTRAIL group,rmhTRAIL plus GEM group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 ± 3.04, 2.53 ± 1.25,4.52 ± 2.87, and 1.69 ± 0.97, respectively, all significantly smaller than that of the negative control group （ 8.82 ±. 5.62, P 〈 0.05 or P〈0.01）. The tumor weight of these four groups were （2.23 ±0.29） g, （1.12±0.77） g, （2.51 ±0.87） g, and 0.60 ± 0. 18 g, respectively, all significantly less then that of the negative control, group （4.71 g ±0.97 g, all P 〈0.01 ）. Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were significantly smaller than those of either rmhTRAIL group or GEM group （ P 〈 0.05 and P 〈 0.01, respectively）. Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM and DDP group were significantly smaller than those of either rmhTRAIL group or GEM plus DDP group （P 〈 0.05 and P 〈 0.01, respectively）. Conclusion The combination of rmhTRAIL and GEM has a synergistic inhibitory effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.