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(recombinant mutant human TRAIL,rmhTRAIL)或称为环化变构TRAIL(circular permuted TRAIL,CPT)与氟尿嘧啶注射液(5-Fluorouracil,5-FU)联用对裸鼠结直肠癌移植瘤的的抗肿瘤作用。方法:将人结直肠癌(human colorectal cancer,CRC)细胞HCT116分别接种于每只裸鼠右侧腋窝中部外侧皮下,建立裸鼠移植瘤模型,随机分组后5-FU采用尾静脉注射给药,CPT以腹腔注射给药,观察裸鼠一般情况,测量其体重及皮下移植瘤长短径,实验结束处死动物后剥取瘤组织、称量瘤重并拍照,采用TUNEL/DAPI法检测细胞凋亡,并应用激光共聚焦显微镜观察。结果:CRC荷瘤裸鼠模型构建成功,荷瘤裸鼠一般情况良好;与对照组相比,单药CPT或5-FU对裸鼠移植瘤的生长均有抑制作用(P<0.01),当两药联用时抑制生长作用更加明显(P<0.01),且以CPT高剂量组最为显著;与对照组比较,CPT和5-FU单药组及联合用药组裸鼠移植瘤的体积及瘤重均明显减小(P<0.05);CPT、5-FU单药及两者联合都促进了肿瘤细胞凋亡,以联合组诱导凋亡作用更加显著,相比对照组差异有显著性(P<0.05)。结论:CPT单药及其联合5-FU能明显抑制裸鼠结直肠癌皮下移植瘤的生长,并能诱导裸鼠移植瘤细胞凋亡。
Objective:To observe the antitumor effect of recombinant mutant human tumor necrosis factor(TNF)-related apoptosis-inducing ligand(rmhTRAIL)or known as circular permuted TRAIL(CPT)in combination with 5-fluorouracil(5-FU)on transplanted tumor of colorectal cancer in nude mice.Methods:Human colorectal cancer(CRC)cell line HCT116 was inoculated subcutaneously into the middle lateral axillary of each nude mouse to establish transplanted tumor model in nude mice.After randomization,5-FU was injected into caudal vein and CPT was injected into abdominal cavity.The general situation of nude mice was observed,and the weight and tumor length and diameter of nude mice were measured.Finally,all the animals were sacrificed,and then the tumor tissues were stripped,photographed and weighed.The tumor cell apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)/24',6-diamidino-2-phenylindole(DAPI)assay,and observed and photographed by Laser confocal microscope.Results:CRC bearing nude mice model was successfully established,and the nude mice were all in good condition.CPT and 5-FU alone could inhibit the growth of transplanted tumor in nude mice,and the comparison of that with control group has statistical difference(P<0.01).The combination of the two drugs had more significant inhibitory effect on the growth of transplanted tumor in nude mice,and the high-dose CPT group was the most significant(P<0.01).In comparison with control group,the tumor volume and weight of CPT,5-FU and co-treatment groups were significantly reduced(P<0.05).CPT,5-FU and their combination promoted the apoptosis of tumor cells,especially in the combination group,and the difference was significant in comparison with control(P<0.05).Conclusion:CPT alone or in combination with 5-FU can significantly suppress the growth of human CRC HCT116 transplanted tumors in nude mice,and promote the apoptosis of tumor cells CRC tumor-bearing nude mice.
作者
孙同友
赵丽霞
崔玉洁
周硕
梁秀军
孙大永
SUN Tongyou;ZHAO Lixia(Chengde Central Hospital, Hebei Chengde 067000, China)
出处
《河北医学》
CAS
2022年第5期731-736,共6页
Hebei Medicine
基金
河北省承德市科技计划项目,(编号:201804A078)
河北省卫生健康委科研基金项目,(编号:20211025)
河北省高等学校科学技术研究项目,(编号:QN2016031)
河北省青年科技计划项目,(编号:20200765)。
关键词
移植瘤
结直肠癌
肿瘤坏死因子相关凋亡诱导配体
裸鼠
Transplanted tumor
Colorectal cancer
Tumor necrosis factor related apoptosis inducing ligand
Nude mice