紫外线诱导SKH-1无毛小鼠皮肤鳞癌模型的构建及DNA-PKcs在小鼠及成人皮肤组织的表达

姜慧; 张娟; 徐丹; 何黎

紫外线诱导SKH-1无毛小鼠皮肤鳞癌模型的构建及DNA-PKcs在小鼠及成人皮肤组织的表达

昆明医科大学第一附属医院皮肤科云南省皮肤病医院

基金项目:

基金：国家自然科学基金资助项目 (81472540, 81660518); 昆明医科大学硕士研究生创新基金资助项目 (2018S092);

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出版历程
- 收稿日期: 2018-11-06

Construction of UV-induced Skin Squamous Cell Carcinoma Model of SKH-1 Hairless Mice and Expression of DNA-PKcs in Mice and Adult Squamous Cell Carcinoma

Funds:

基金：国家自然科学基金资助项目 (81472540, 81660518); 昆明医科大学硕士研究生创新基金资助项目 (2018S092);

摘要

摘要: 目的紫外线照射SKH-1小鼠构建皮肤鳞状细胞癌动物模型, 探讨紫外线诱发皮肤SCC发生及AK向SCC转化过程中DNA-PKcs-m TORC2/Akt信号转导通路的DNA-PKcs活化水平。方法将43只SKH-l无毛小鼠随机分成实验组 (33只) 和对照组 (10只) 。实验组采用SUV-1000日光模拟器模拟日光照射SKH-1无毛鼠, 对照组不做任何处理。在第12、18、24、28周分别处死小鼠行皮肤组织病理检查。28周取同一只小鼠背部不同皮损行组织病理检查和免疫组化检测。收集成人日光性角化病 (AK) 、皮肤鳞状细胞癌 (SCC) 、正常避光部位 (NNS) 、正常曝光部位 (NES) 皮肤组织各5例, 进行后续Western Blot验证。结果 12周后实验组部分小鼠背部皮肤增厚, 皮棘隆起;17周开始实验组小鼠背部皮肤陆续出现直径≥l mm的丘疹;照射28周后成瘤率达100%;对照组未见肿瘤形成。DNA-PKcs和p-DNA-PKcs (T2609) 均细胞定位于细胞质和细胞核, 小鼠表皮组织中DNA-PKcs表达含量增加, 统计学分析有差异 (P<0.05) , 而p-DNA-PKcs (T2609) 无差异 (P>0.05) 。人表皮组织中DNA-PKcs和p-DNA-PKcs (T2609) 表达含量均增加且有统计学分析差异 (P<0.05) 。结论成功制备小鼠AK模型和SCC模型;明确了紫外线诱导皮肤鳞状细胞癌的过程中, 可诱发DNA损伤及修复等过程。
- 紫外线 /
- 皮肤鳞状细胞癌 /
- 日光性角化病 /
- 动物 /
- 疾病模型 /
- DNA-PKcs
Abstract: Objective To construct an animal model of squamous cell carcinoma of the skin in SKH-1 mice with ultraviolet irradiation, and to investigate the DNA-PKcs activation level of DNA-PKcs-m TORC2/Akt signal transduction pathway during UV-induced skin SCC and AK to SCC transformation. Methods 43 SKH-l hairless mice were randomly divided into experimental group (33) and control group (10) .The experimental group used the SUV-1000 solar simulator to simulate sun-irradiated SKH-1 hairless mice, and the control group did not intervene. Experimental group 1 maintained irradiation for 24 weeks, and experimental group 2 maintained irradiation for 16 weeks. The mice were sacrificed at 12, 18, 24, and 28 weeks for skin histopathological examination. At 28 weeks, the same skin of the same mouse was taken for histopathological examination and immunohistochemistry.Five cases of adult solar keratosis (AK) , cutaneous squamous cell carcinoma (SCC) , normal light-protected site (NNS) , and normal exposed site (NES) were collected for Western Blot. Results After 12 weeks, some mice in the experimental group were thickened in the back skin. At 17 weeks, the papules with diameter ≥ 1 mm appeared in the back skin of experimental group. After 28 weeks of irradiation, the tumor formation rate reached100%. No tumor formation was observed in the control group. Both DNA-PKcs and p-DNA-PKcs (T2609) were localized in the cytoplasm and nucleus. Expression of DNA-PKcs increased in epidermal tissue. There was a difference in the statistical analysis of DNA-PKcs expression (P<0.05) , but there was no difference in the expression of p-DNA-PKcs (T2609) (P>0.05) .The expression levels of DNA-PKcs and p-DNA-PKcs (T2609) in human epidermal tissue increased and there were statistical differences (P<0.05) .Conclusions We successfulyl prepared of mouse AK model and SCC model. It is clear that UV-induced squamous cell carcinoma of the skin can induce DNA damage and repair.
- Ultraviolet radiation /
- Squamous cell carcinoma /
- Actinic keratosis /
- Disease models /
- Animal /
- DNA-PKcs

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参考文献(14)

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