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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。
Objective To evaluate the antitumor effect of newly constructed recombinant allosteric human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (recombinant muruthuman TRAIL, rmhTRAIL). Methods Non-small cell lung cancer NCI-H460 xenograft model in nude mice was used to observe the effect of rmhTRAIL with different doses (divided into 5 groups) on tumor growth inhibition in nude mice. In addition, the apoptosis induced by rmhTRAIL in nude mice tumor cells in vitro and in vivo was observed by TUNEL staining and gel electrophoresis of DNA fragments. Results The relative tumor volume (RTV) of rmhTRAIL (5mg / kg) and high dose (15mg / kg) groups were 3.19 ± 2.05 and 1.47 ± 0.77 respectively, significantly lower than those of the control group (8.48 ± 5.87, P < ; Relative tumor rate of increase (T / C%) were 37.6% and 17.3%. The tumor weights of medium dose group and high dose group were 1.09g ± 0.55g and 0.31g ± 0.09g, respectively, which were significantly lower than those of the control group (2.78g ± 0.77g, P <0.01). A large number of apoptotic TUNEL-positive cells appeared in rmhTRAIL-treated tumor cells and in vitro cultured tumor cells. DNA extracts of rmhTRAIL-treated tumor cells showed typical DNA ladder with apoptosis characteristics on agarose gel electrophoresis . Conclusion rmhTRAIL has significant antitumor activity in vitro and in vivo, and its mechanism is mainly to cause apoptosis of tumor cells.