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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。
Objective To investigate the inhibitory effect of arsenic trioxide (As2O3) on the growth of human nasopharyngeal carcinoma with poorly differentiated squamous cell carcinoma in BALB / C nude mice and its mechanism, and to observe its differentiation-inducing effect on nasopharyngeal carcinoma cells. Methods CSNE-1 nasopharyngeal carcinoma cell lines were inoculated into nude mice to construct xenograft model. Intraperitoneal injection of As2O3 (5 mg / kg). The morphological changes of the xenografts were observed under light microscope and electron microscope. The apoptosis rates were calculated by TUNEL staining. The expressions of PCNA, p53, Bcl-2 and bax were detected by immunohistochemistry. Results After As2O3 was administered intraperitoneally, the growth of the transplanted tumor of BALB / C nude mice of nasopharyngeal carcinoma was inhibited. The density of cancer cells in the tumor tissue was reduced, the cell shrinkage, erythrome staining in cytoplasm and gradual maturation of tumor tissues were observed. The keratinocytes and keratinocytes ; Interstitial connective tissue increased. Tumor cells under the TEM showed mature differentiation and obvious keratinization. The number of tiny protrusions on the surface of the cells increased, the number of desmosomes increased and the desmosomes were connected to each other. The proportion of nuclear cytoplasm decreased, and a large number of fibrils appeared in the cytoplasm around the perinuclear area. TUNEL examination showed that apoptotic cells increased; wild-type p53 and baX were highly expressed, PCNA was low, and Bcl-2 was unchanged. Conclusion As2O3 can induce the differentiation and apoptosis of xenografted human nasopharyngeal xenografts in nude mice, which may be related to the high expression of p53 and bax, but not to Bcl-2.