摘要
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.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2008年第11期808-812,共5页
Chinese Journal of Oncology