摘要
背景与目的:既往研究发现三氧化二砷(As2O3)可诱导白血病细胞的分化,但对实体瘤细胞的诱导分化作用报道甚少。本实验拟探讨As2O3对人鼻咽低分化鳞癌可移植瘤在BALB/C裸鼠体内生长的影响,重点观察其诱导鼻咽癌细胞分化的作用。方法:以人鼻咽低分化鳞癌鼠移植癌细胞株CSNE-1为研究对象,观察腹腔注射As2O3(5mg·kg-1·d-1连续10天后,每周给药3次,连续3周)对人鼻咽癌移植瘤在BALB/C裸鼠体内生长情况的影响。用光学显微镜和电子显微镜观察移植瘤细胞形态变化,用免疫组化法检测瘤组织中增殖细胞核抗原(PCNA)的表达情况。结果:腹腔注射As2O3后,人鼻咽癌BALB/C裸鼠移植瘤生长被抑制,抑瘤率为75.4%。同时,瘤组织中癌细胞密度减少,细胞皱缩,胞浆红染,瘤组织分化渐成熟,出现角化细胞和角化珠;间质结缔组织增多。透射电镜下肿瘤细胞出现成熟分化及明显角质化,细胞表面微小突起增多,细胞间桥粒增多并以桥粒互相连接,细胞核浆比例减少,胞浆中出现大量张力原纤维并围绕核周。癌细胞PCNA在阴性对照组呈高表达,PI(PCNA阳性细胞指数)为(95.2±5.0)%,而As2O3组癌细胞PCNA表达明显减少,PI为(53.6±7.0)%(P<0.001)。结论:As2O3抑制人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的生长,这种抑制作用可能与其诱导癌细胞向成熟方向分化有关?
BACKGROUND &OBJECTIVE:There is evidence that arsenic trioxide (As 2 O 3 )induce differentiation of leukemia cells;however,little is known about its effect on solid tumors.The aim of this study was to investig ate w hether AS 2 O 3 can induce cell differentiation and its association with g rowth inhibit ion in human nasopharyng eal carcinoma usi ng BALB /C nude mice xenog raft model.METHODS :Poorly differentiated human nasopharyng eal squamous carcinoma cells from CSNE-1cell strain were tr ansplanted subcutaneously to BALB /C nude mice to produce tumors.As 2 O 3 at a dose of 5mg ·(kg·d) -1 was g iven intraperitoneally for 10consecutive days,and then 3times a week for the following 3weeks.The xenog raft tum or g rowth in mice was observed after d rug administration.The morpholog ical chang es of the tumors were examined u nder lig ht and electron microscopy.Prol iferating cell nuclear antig en(PCNA)expression was determined by immunohistochemistry.RESULTS :As 2 O 3 at dose of 5mg ·(kg·d) -1 sig nificantly inhibited the tumor g rowth in vivo,with a inhibitory rate of 75.4%.Remarkabl e cell differentiation induced by As 2 O 3 was observed under lig ht microscope and transmission electron microscope ,which was characterized by keratinizatio n of tumor cells,decreased nuclear /cytoplasm ratio,increased cytopla smic org anelles and rich tonofibril s in cytoplasm.Desmosomes and micro-pr ocesses were much more frequently observed in tumors treated with As 2 O 3 .Sig nificantly decreased PCNA expr ession was observed in As 2 O 3 -treated tumor cells.The PCNA-posi tive cell index(PI )was 53.6±7.0%in As 2 O 3 -treated mice,and 95.2±5.0%in cont rol,respectively(P<0.001).CONCLUSION:The g rowth of human nasopharyng eal carcinoma xenog raft in BALB /C nude mice can be s ig nificantly inhibited by As 2 O 3 ,which mig ht be related to the cell differen tiation induced by As 2 O 3 .
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第1期21-25,共5页
Chinese Journal of Cancer
关键词
三氧化二砷
诱导
鼻咽低分化鳞癌
裸鼠
移植瘤
细胞分化
Arsenic trioxide (As_2O_3)
Nasopharyng eal neoplasm
BALB /C nude mice
Xenog raft
Induced differentiation
