【摘要】 目的观察新研制的重组变构人肿瘤坏死因子相关的凋亡诱导配体(TRAIL)(recombinantmutanthumanTRAIL,rmhTRAIL)的抗肿瘤作用进行评价。方法采用非小细胞肺癌NCI-H460裸鼠异种移植瘤模型,观察腹腔注射不同剂量(共分5组)的rmhTRAIL对裸鼠肿瘤生长抑制的作用。此外,用TUNEL染色法及DNA片段的凝胶电泳法观察了rmhTRAIL在体内外对裸鼠肿瘤细胞的诱导凋亡作用。结果rmhTRAIL中(5mg/kg)、高剂量(15mg/kg)组相对肿瘤体积(RTV)分别为3.19±2.05和1.47±0.77,显著小于对照组8.48±5.87(P<0.05,和P<0.01);相对肿瘤增值率(T/C%)分别为37.6%和17.3%。中、高剂量组肿瘤重量分别为1.09g±0.55g和0.31g±0.09g,显著小于对照组2.78g±0.77g(P<0.01)。经rmhTRAIL处理的肿瘤组织和体外培养的肿瘤细胞均出现大量TUNEL染色阳性的凋亡细胞,rmhTRAIL处理的肿瘤细胞的DNA提取物在琼脂糖凝胶电泳上呈现典型的具有凋亡特征的DNA梯带。结论rmhTRAIL具有显著的体内外抗肿瘤作用,其机制主要是引起肿瘤细胞的凋亡。更多还原

【Abstract】 Objective To evaluate the therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) on non-small cell cancer (NSCLC). Methods NSCLC cells of the line NCI-H460 were cultured and underwent agarose gel electrophoresis. rmhTRAIL of different concentrations was added into the culture fluid to observe the influence of rmhTRAIL. Nude BALB/c rats were transplanted with rat NCI-H460 tumor. Then the rats carrying xenografts were randomly divided into 5 groups of 8 rats: negative control group to be injected intraperitoneally with normal saline; positive control group to be injected with vancristine; low-dose rmhTRAIL group, to be injected with 1.7 mg/kg rmhTRAIL, middle-dose rmhTRAIL group to be injected with rmhTRAIL 5.0 mg/kg, and high-dose rmhTRAIL group to be injiected with 15.0 mg/kg rmhTRAIL. The size of tumor was measured every 3~4 days. Ten days after the administration of different drugs the rats were killed and the tumors were taken out to undergo TUNEL staining for microscopy. Results The relative tumor volume of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 3.19±2.05 and 1.47±0.77 respectively, both significantly smaller than that of the negative group (8.48±5.87, P <0.05 and P <0.01). The relative tumor growth rate of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 37.6% and 17.3% respectively. The tumor weight of low-dose rmhTRAIL group and high-dose rmhTRAIL group were 1.09 g±0.55 g and 0.31 g±0.09 g respectively, both significantly lighter than that of the negative control group (2.78±0.77, both P <0.01). Large amount of apoptotic cells were seen in the tumor tissues of the rmhTRAIL -treated rats and tumors cells cultured with rmhTRAIL. Agarose gel electrophoresis showed apoptosis-characteristic ladder in the DNA extracted from the rmhTRAIL -treated tumors cells. Conclusion rmhTRAIL dose-dependently inhibit the growth of NSCLC cells, primarily by inducing apoptosis of tumor cells.更多还原