摘要
[目的]考察三氧化二砷(arsenic trioxide,As2O3)联合丹参酮对肝癌裸鼠移植瘤的作用效果并初步探讨其可能的分子机制。[方法]建立裸鼠人肝癌移植瘤模型,待瘤体生长到体积100mm3左右,将裸鼠随机分为5组,分别为模型对照组、As2O3单用组(As2O3低剂量组,2.5mg/kg)、阳性对照组(As2O3高剂量组,5.0mg/kg)、丹参酮单用组(500mg/kg)、As2O3-丹参酮组(As2O32.5mg/kg+丹参酮500mg/kg),每组8只,每天腹腔注射给药,共19d。比较各组肿瘤生长曲线和瘤体质量;采集血液进行血常规和生化常规分析;以原位末端转移酶标记(TdT-mediated dUTP nick end labeling, TUNEL)法检测瘤体组织细胞凋亡情况;免疫组化和Western blot检测凋亡相关蛋白的表达。[结果]随着给药时间的延长,与模型对照组比较,As2O3单用组、丹参酮单用组、As2O3-丹参酮组以及阳性对照组均表现出一定的抑瘤效果(P<0.01)。与阳性对照组比较,As2O3-丹参酮组的抑瘤效果更显著(P<0.05)。与模型对照组比较,As2O3单用组、阳性对照组、As2O3-丹参酮组白细胞(white blood cell,WBC)计数均上调,其中As2O3单用组差异具有统计学意义(P<0.05);As2O3单用组、阳性对照组红细胞(red blood cell,RBC)计数显著下调(P<0.05,P<0.01);各治疗组血红蛋白(hemoglobin,HGB)水平均下调,其中阳性对照组差异有统计学意义(P<0.01);As2O3单用组、阳性对照组、As2O3-丹参酮组血小板(platelet,PLT)计数均上调,其中As2O3单用组和阳性对照组差异具有统计学意义(P<0.01);与阳性对照组比较,As2O3-丹参酮组WBC、RBC计数和HGB水平均上调,但差异无统计学意义(P>0.05)。与模型对照组比较,As2O3单用组、阳性对照组与As2O3-丹参酮组丙氨酸氨基转移酶(alanine aminotransferase,ALT)水平上调,但差异无统计学意义(P>0.05);各治疗组中天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平下调,其中丹参酮单用组差异有统计学意义(P<0.01);各治疗组中
[Objective]To investigate the effect of arsenic trioxide(As2O3) combined with tanshinone on transplanted hepatocellular carcinoma in nude mice and explore its possible molecular mechanism. [Methods]Human liver cancer transplantation tumor model was established in BALB/C-nu mice. When the tumor body grew to a volume of about 100 mm3, the nude mice were randomly divided into five groups: Model control group, As2O3 single-use group(As2O3 low-dose group, 2.5 mg/kg), positive control group(As2O3 high-dose group,5.0 mg/kg), tanshinone single-use group(500 mg/kg), and As2O3-tanshinone group(As2O32.5 mg/kg+tanshinone 500 mg/kg), with 8 mice in each group. All mice were injected intraperitoneally every day for 19 days. The growth curve and weight of tumor were compared in each group;blood samples were collected for blood routine and biochemical analysis;apoptotic status of tumor tissues was detected by TdT-mediated dUTP nick end labeling(TUNEL);expression of apoptotic-related proteins was detected by immunohistochemistry and Western blot. [Results]With the prolongation of administration time, compared with model control group, As2O3 single-use group, tanshinone singleuse group, As2O3-tanshinone group and positive control group all showed a certain anti-tumor effect(P<0.01). Compared with positive control group, the effect of As2O3-tanshinone group was more obvious(P <0.05).Compared with model control group, the white blood cell(WBC) count of As2O3 single-use group, positive control group, and As2O3-tanshinone group increased, the difference of As2O3 single-use group was statistically significant(P<0.05);the red blood cell(RBC) count of As2O3 single-use group and positive control group decreased, the difference was statistically significant(P <0.05, P <0.01);the hemoglobin(HGB) level of all treatment groups decreased, and the difference of positive control group was statistically significant(P <0.01);the platelet(PLT) count of As2O3 single-use group, positive control group, As2O3-tanshinone group increased, the difference
作者
廖广辉
张广顺
楼招欢
程汝滨
张光霁
LIAO Guanghui;ZHANG Guangshun;LOU Zhaohuan(College of Pharmacy,Zhejiang Chinese Medical University,Hangzhou(310053),China)
出处
《浙江中医药大学学报》
CAS
2020年第1期15-23,共9页
Journal of Zhejiang Chinese Medical University
基金
浙江省教育厅高校访问学者教师专业发展项目(FX2016019)
国家自然科学基金面上项目(81573962)
浙江中医药大学药学院时珍青年人才培养计划资助项目(SZZ201812)~~
关键词
AS2O3
丹参酮
肝癌
细胞凋亡
裸鼠移植瘤
增效减毒
arsenic trioxide
tanshinone
liver cancer
cell apoptosis
nude mouse transplantation tumor
increased efficacy and reduced toxicity
