摘要
目的构建具有肿瘤包绕型血管(VETC)的小鼠肝细胞癌(肝癌)模型,探讨索拉非尼对VETC(+)肝癌的影响。方法将49只C57小鼠随机分为预防组(15只)、治疗组(15只)和对照组(19只)。预防组小鼠肝包膜下接种HEP1-6肝癌细胞(5×10^(5)/只),2 d后开始连续索拉非尼溶液灌胃(25 mg/kg,每日一次);治疗组于接种后10 d开始连续予索拉非尼溶液灌胃(50 mg/kg,每日一次);对照组以相同体积的DMSO灌胃,于接种后5、10、15、20、23、27 d分批处死小鼠,肿瘤组织石蜡包埋,切片行CD34及HE染色,观察小鼠体重及不良反应,记录成瘤情况、肿瘤最大径等。肿瘤最大径及VETC环数等比较采用Kruskal-Wallis检验。结果各组小鼠均顺利成瘤,接种后20 d对照组2只小鼠肝内可见转移灶,接种后23 d对照组1只小鼠死于肿瘤进展。治疗组与预防组均未观察到明显肝内转移,小鼠可见脱屑,无明显厌食、腹泻等不良反应,体重无明显变化,饲养笼干燥,无死亡。预防组接种后5、10、15、20、23 d肿瘤最大径均明显小于对照组(H=-4.355,-3.857,-6.000,-6.250,-6.167;P<0.05);接种后15 d,治疗组肿瘤最大径亦明显小于对照组(H=-5.125,P<0.05)。接种后5 d,对照组小鼠肝肿瘤中均可观察到明显的VETC结构;接种后15 d VETC环数较5 d明显减少(H=-3.857,P<0.05),且肿瘤内部均出现大片坏死灶;接种后23 d VETC环数较15 d明显增多(H=4.582,P<0.05)。预防组接种5~23 d VETC形成明显被抑制;5、10、20 d VETC环数均明显少于对照组(H=-3.971,-4.355,-6.369;P<0.05)。结论本研究成功构建小鼠VETC(+)肝癌模型。索拉非尼可有效降低小鼠肝癌的肿瘤负荷,破坏VETC结构并抑制其形成,预防组疗效尤为显著。
Objective To establish a mouse model of hepatocellular carcinoma(HCC)with vessels encapsulating tumor clusters(VETC)and to evaluate the effect of sorafenib on VETC(+)HCC.Methods 49 C57 mice were randomly divided into the prevention(n=15),treatment(n=15)and control groups(n=19).In the prevention group,HEP1-6 HCC cells were inoculated under the liver capsule with a dosage of 5×10^(5) cells per mouse,and after 2 d,sorafenib solution was continuously administered by gavage(25 mg/kg,once daily).In the treatment group,sorafenib solution was continuously given by gavage(50 mg/kg,once daily)at 10 d after inoculation.In the control group,an equivalent amount of DMSO was given by gavage.Mice were sacrificed at 5,10,15,20,23 and 27 d after inoculation,respectively.The tumor tissues were embedded in paraffin and sliced up for CD34 and HE staining.The weight and adverse reactions of mice were observed.The tumor formation and maximum tumor diameter were recorded.The maximum tumor diameter and number of VETC rings were compared by Kruskal-Wallis test.Results All the mice in the groups successfully developed tumors.At 20 d after inoculation,2 mice had intraheptic metastatic lesions in the control group,and 1 mouse died of tumor progression at 23 d after inoculation.No evident intrahepatic metastasis was observed in the treatment and prevention groups.Desquamation was observed in the mice.No obvious adverse reactions,such as anorexia and diarrhea,were seen.No significant change in weight was noted.The mouse cage was dry and no mouse died.In the prevention group,the maximum tumor diameter was significantly smaller than those in the control group at 5,10,15,20 and 23 d after inoculation(H=-4.355,-3.857,-6.000,-6.250,-6.167;P<0.05).At 15 d after inoculation,the maximum tumor diameter in the treatment group was significantly smaller than that in the control group(H=-5.125,P<0.05).At 5 d after inoculation,evident VETC structure could be observed in mouse liver tumors in the control group.At 15 d after inoculation,the number of VETC r
作者
熊培尧
唐雨豪
杨子良
朱应钦
王骏成
徐立
Xiong Peiyao;Tang Yuhao;Yang Ziliang;Zhu Yingqin;Wang Juncheng;Xu Li(Department of Hepatic Surgery,Sun Yat-sen University Cancer Center,Guangzhou 510060,China)
出处
《中华肝脏外科手术学电子杂志》
CAS
2022年第3期315-319,共5页
Chinese Journal of Hepatic Surgery(Electronic Edition)
基金
国家自然科学基金(81772589)。
关键词
癌
肝细胞
肿瘤包绕型血管
索拉非尼
小鼠
Carcinoma,hepatocellular
Vessels encapsulating tumor clusters(VETC)
Sorafenib
Mouse
