注射用核糖核酸Ⅱ联合环磷酰胺对肉瘤细胞S180荷瘤小鼠肿瘤的抑制作用及对生存影响的研究

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目的:探讨注射用核糖核酸Ⅱ(简称:核糖核酸Ⅱ)与化疗药物环磷酰胺(CTX)联合对肉瘤细胞S180荷瘤小鼠肿瘤抑制作用及对小鼠生存的影响。方法:分别建立肉瘤细胞S180实体移植瘤小鼠模型和腹腔积液瘤小鼠模型。将CTX(25 mg/kg,1次/2 d)单独或联合低剂量(25 mg/kg,1次/d)、中剂量(50 mg/kg,1次/d)核糖核酸Ⅱ腹腔注射实体移植瘤小鼠10 d,将CTX(25 mg/kg,1次/2 d)单独、中剂量(50 mg/kg,1次/d)或高剂量(100 mg/kg,1次/d)核糖核酸Ⅱ单独或联合CTX(25 mg/kg,1次/2 d)腹腔注射腹腔积液瘤小鼠至全部死亡,两模型均设未经药物处理的模型组,各组小鼠均为8只。对于实体移植瘤小鼠,给药后称量体质量,测量活体肿瘤体积,处死小鼠后取肿瘤组织并称量其质量,计算抑瘤率。对于腹腔积液瘤小鼠,给药后称量体质量,计算体质量增长率,绘制各组生存曲线,计算生命延长率。结果:(1)实体移植瘤小鼠:给药后各给药组小鼠体质量均低于模型组。给药期间,模型组活体肿瘤体积均远超各给药组;给药第8天起,CTX组活体肿瘤体积开始大于两个联合给药组。给药结束处死小鼠后称量显示,各给药组肿瘤质量均低于模型组(均n P<0.01),CTX+核糖核酸Ⅱ低剂量组和CTX+核糖核酸Ⅱ中剂量组的肿瘤质量均低于CTX组(均n P<0.05),两组抑瘤率均高于CTX组(83.6%、77.2%比58.5%)。(2)腹腔积液瘤小鼠:给药12 d后,CTX组小鼠体质量增长率迅速增加,达最高,两个联合给药组小鼠体质量增长率较其他各组均低。核糖核酸Ⅱ高剂量组与CTX组小鼠生命延长率分别为48.2%、53.2%,对生命延长作用相当;核糖核酸Ⅱ中剂量组小鼠生命延长率仅20.9%;CTX+核糖核酸Ⅱ中剂量组和CTX+核糖核酸Ⅱ高剂量组小鼠生命延长率分别达到94.2%、105.0%。n 结论:核糖核酸Ⅱ联合CTX可明显延长肉瘤细胞S180荷瘤小鼠生存时间,提高抑瘤率,改善小鼠生命质量,二者具有协同增效作用。“,”Objective:To investigate the effects of ribonucleic acid for injection Ⅱ, often called RNA Ⅱ for short, combined with chemotherapeutic drug cyclophosphamide (CTX) on the tumor inhibition and survival of sarcoma cell S180 tumor-bearing mice.Methods:The solid transplanted tumor mouse model of sarcoma cell S180 and peritoneal fluid tumor mouse model were established respectively. CTX (25 mg/kg, once for 2 days) alone or combined with low-dose (25 mg/kg, once a day) and medium-dose (50 mg/kg, once a day) RNA Ⅱ were injected intraperitoneally into solid transplanted tumor mice for 10 d. CTX (25 mg/kg, once for 2 days) alone, medium-dose (50 mg/kg, once a day) or high-dose (100 mg/kg, once a day) RNA Ⅱ alone or combined with CTX were injected intraperitoneally into peritoneal effusion tumor mice until all mice died. The two models were set up for modeling groups without drug treatment, 8 mice in each group. The body mass of solid transplanted tumor mice after administration was weighed, the tumor tissue in vivo was taken out and weighed after the mice were executed, and the tumor inhibition rate was calculated. The body mass of peritoneal effusion tumor mice after administration was weighed, the growth rate of body mass was calculated, the survival curve of each group was drawn, and the life extension rate was calculated.Results:(1) Solid transplanted tumor mice: the body mass of mice in each administration group was lower than that in the modeling group after administration. During the administration period, the tumor volume in the modeling group was much higher than that in each administration group. From the 8th day of administration, the tumor volume in vivo in the CTX group began to be larger compared with that in the two combined administration groups. After stopping the administration and killing the mice, the weighing showed that the tumor mass of each administration group was lower than that in the modeling group (all n P < 0.01), the tumor mass of CTX + RNA Ⅱ low-dose group and CTX + RNA Ⅱ medium-dose group was lower than that of CTX group (all n P < 0.05), and the tumor inhibition rate of the two groups was higher than that of CTX group (83.6%, 77.2% vs. 58.5%). (2) Peritoneal effusion tumor mice: after administration for 12 d, the body mass growth rate of mice in CTX group was increased rapidly and reached the highest, and the body mass growth rate of mice in the two combined administration groups was lower than that in other groups. The life prolongation rates of RNA Ⅱ high-dose group and CTX group were 48.2% and 53.2% respectively, which had the same effect on life prolongation. The life prolongation rate in RNA Ⅱ medium-dose group was 20.9%. The life prolongation rates of CTX + RNA Ⅱ medium-dose group and CTX + RNA Ⅱ high-dose group were 94.2% and 105.0% respectively.n Conclusions:RNA Ⅱ combined with CTX can significantly prolong the survival time of sarcoma cell S180 tumor-bearing mice, increase the tumor inhibition rate and improve the quality of life of the mice. Both of them have a synergistic effect.
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