光催化纳米二氧化钛对人鼻咽癌裸鼠模型的治疗研究  

Therapeutic effects of photocatalytic nano-TiO2 on human nasopharyngeal carcinoma xenografts innude mice

作　　者：包伟晶[1] 林丛[1] 李志春[1] 林昶[1] 吴敏霞[1] 钟秀容[1] 

机构地区：[1]福建医科大学附属第一医院耳鼻咽喉科,福州350004

出　　处：《中华耳鼻咽喉头颈外科杂志》2012年第7期581-586,共6页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

摘　　要：目的研究光催化纳米二氧化钛（TiO：）对人鼻咽癌裸鼠移植瘤模型的治疗效果，初步探讨其抑癌机制。方法建立荷人鼻咽癌裸鼠移植瘤模型，随机分成6组，包括实验组：3个梯度含量的纳米TiO2＋紫外光照射组；阴性对照组：单纯纳米TiO2组与单纯紫外光照射组；空白对照组。其中纳米TiO2，悬液采用瘤内注射，经波长范围330～400nm的紫外光处理后24h，取各组瘤组织HE染色作病理分析；透射电镜观察肿瘤细胞超微结构的变化及凋亡情况；采用免疫组化检测肿瘤组织Caspase-3的表达，采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法（TUNEL）检测细胞凋亡情况，并分析两者的相关性。结果病理学分析，纳米TiO2光催化治疗后移植瘤组织的局部炎性反应明显（II、Ⅲ级），伴随炎性反应的是局部坏死灶形成；而阴性及空白对照组无明显炎性反应（I级）。透射电镜下观察，实验组可见纳米TiO2颗粒广泛进入胞质胞核，肿瘤细胞多有凋亡的形态学改变。实验组Caspase．3的阳性表达及TUNEL标记的阳性细胞数显著多于对照组（P〈0．01），且阳性表达随TiO2含量递增而增强（P〈0．01）。结论光催化纳米TiO2可通过提高移植瘤组织的Caspase一3表达活性来诱导细胞凋亡，抑制肿瘤生长，且效果在一定范围内呈TiO2含量依赖性。光催化纳米TiO2通过诱导肿瘤细胞凋亡和介导炎性反应是其发挥抑癌作用的可能机制。Objective To study the therapeutic effect of photocatalytic nano-TiO2 on nasopharyngeal carcinoma xenograft in nude mice and underlying mechanism. Methods Nude mice bearing human nasopharyngeal carcinoma xenograft were randomly divided into six groups： nano-Ti02 ＋ UV irradiation（ with gradient concentration of nano-TiO2 ） ; nano-TiO2 alone and UV irradiation alone and blank control. The nano-TiO2 suspension was injected into xenografts, and 24 h after UV light with the wave length of 330 - 400 nm, all the xenografts were removed and sectioned for HE staining. Ultrastructure and apoptosis of tumor cells in the xenografts were observed by transmission electron microscope （TEM）. The expression of Caspase-3 was examined immunohistochemical staining and the apoptosis was detected with TUNEL. Results Pathological analysis showed significant inflammatory responses （ grade 11 and ]II ） with local necrosis occurred in tumor tissues after nano-Ti02 photodynamic therapy, but not in the negative control and blank control. TEM showed the nano-TiO： particles entered into the cytoplasm and the nucleus of tumor cells and many tumor cells had morphological changes for apoptosis. Significant positive expression of Caspase-3 and TUNEL-positive cells were found in the the xenograts with the treatments of nano-TiO2 ＋ UV irradiation compared to control（P 〈0.01） , which were enhanced with the increases in nano-TiO2 concentration （P 〈 0. 01 ）. Conclusion Photocatalytic nano-TiO2 can inhibit the growth of nasopharyngeal carcinoma xenograft in nude mice by inducing Caspase-3 expression and apoptosis in the tumor cells.

关 键 词：催化作用 钛 鼻咽肿瘤 纳米技术 半胱氨酸天冬氨酸蛋白酶3 细胞凋亡 

分 类 号：R739.63[医药卫生—肿瘤]