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

目的 探讨三氧化二砷(As2O3)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As2O3(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As2O3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As2O3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 (As2O3) 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 As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic 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. Results: The cell growth and proliferate activity were significantly inhibited by As2O3 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 observed by TUNEL assay. Over expression of p53 and Bax was detected in the As2O3 treatment group when compared with control group. Conclusion: As2O3 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.