三氧化二砷诱导人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的细胞分化和凋亡的研究(英文)

目的探讨三氧化二砷(As_2O_3)对人鼻咽低分化鳞癌可移植瘤在 BALB/C 裸鼠体内生长的抑制作用并探讨其机制,重点观察其对鼻咽癌细胞的分化诱导作用。方法 CSNE-1鼻咽癌细胞株接种于裸鼠体内构建移植瘤模型。腹腔注入 As_2O_3(5 mg/kg)。光镜及电镜观察移植瘤的形态学变化,TUNEL 染色计算凋亡率,应用免疫组化法检测 PCNA,p53,Bcl-2和 bax 基因的表达。结果腹腔注射 As_2O_3后,鼻咽癌 BALB/C 裸鼠移植瘤生长抑制,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。TUNEL 检查提示凋亡细胞增多;用药后野生型 p53及 bax 高表达,PCNA 低表达,Bcl-2无变化。结论 As_2O_3能诱导人低分化鼻咽裸鼠移植瘤分化和凋亡,可能与 p53及 bax 高表达相关,与 Bcl-2无关。

Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

Objective:To study the effect of arsenic trioxide(As_2O_3)on human poorly differentiated na- sopharyngeal cancer cell line,CSNE-1,in vivo and its possible mechanism of action.Methods:CSNE-1 cells were established as xenografts in BALB/C nude mice.The tumor-bearing mice were treated with As_2O_3 at the dose of 5 mg/kg every day.The tumor growth was observed by tumor-growth curve.Mor- phologic changes were studied under light microscopy and electron microscopy.TUNEL was used to detect apoptosis.The expression of PCNA,p53,Bcl-2 and Bax were determined by immunohistochemistry.Re- sults:The cell growth and proliferate activity were significantly inhibited by As_2O_3 at the dose of 5 mg/kg every day.Morphologic changes such as the formation of keratinization of tumor cells,decreased ratio of nuclear/cytoplasm,increased organelle and plasmic fibril in cytoplasm were identified.Cytodesma,desmo- somes and micro-process were seen under light microscopy and transmission electron microscopy,which revealed that the cancer cells underwent differentiation.In addition,remarkable cell apoptosis were ob- served by TUNEL assay.Over expression of p53 and Bax was detected in the As_2O_3 treatment group when compared with control group.Conclusion:As_2O_3 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis,which may be related to the up-regulation of p53 and Bax expression.