4NQO诱导大鼠舌黏膜癌变过程中HSF1的表达及意义

›› 2016, Vol. 7 ›› Issue (3): 129-133.

4NQO诱导大鼠舌黏膜癌变过程中HSF1的表达及意义

李传祝¹,王飞²,王琼³,刘来奎³

1. 南京医科大学附属口腔医院基础教研室
2. 安徽医科大学无锡临床学院口腔系
3. 南京医科大学口腔研究所

收稿日期:2016-06-11 修回日期:2016-08-03 出版日期:2016-09-25 发布日期:2016-09-28
通讯作者: 刘来奎 E-mail:my_yunkong@njmu.edu.cn
基金资助:
国家自然科学基金;江苏高校优势学科建设工程资助项目

Expression and significance of HSF1 in 4NQO-induced rat tongue carcinogenesis

Received:2016-06-11 Revised:2016-08-03 Online:2016-09-25 Published:2016-09-28

摘要/Abstract

摘要： 目的：探讨热休克因子1（HSF1）在四硝基喹啉-1-氧化物（4NQO）饮水法诱导大鼠舌黏膜癌变过程中的表达及意义。方法：80只Wistar大鼠随机分两组，实验组用0.001%～0.004% 4NQO递增性喂养大鼠8～28周，对照组则用普通自来水喂养，分别于8、16、20、24、28周处死大鼠，通过大体标本、HE染色观察大鼠舌部组织学改变，同时采用免疫组化染色方法观察HSF1在大鼠舌癌变全过程的表达情况。结果：随4NQO作用时间延长和浓度递增，大鼠舌背后部黏膜相继出现颗粒状、白色斑块、疣状突起、菜花状新生物和溃疡状改变。诱导后8、16、20、24、28周，舌癌的发生率分别为0、20.0%、50.0%、66.7%、100%。HSF1在对照组大鼠舌背黏膜上皮中不表达或者微弱表达，而在实验组随着大鼠舌黏膜异常增生程度的增加，HSF1表达明显增强；在原位癌中，HSF1弥漫分布于整个癌巢中；在舌黏膜浸润癌中HSF1在癌上皮中表达有所降低，而在癌基质成纤维细胞中HSF1表达增强。结论：4NQO饮水法可诱导大鼠舌黏膜发生癌变，成功建立大鼠舌癌模型，同时HSF1在大鼠舌癌发生、发展过程中发挥重要作用。

Abstract: Objective： To explore the and significance of heat shock factor 1 (HSF1) in 4-nitroquinoline 1-oxide (4NQO) induced rat tongue carcinogenesis. Methods：A total of 80 Wistar rats were randomly divided into two groups. Rats in experiment group were administered orally with 0.001%-0.004% 4NQO for 8-28 weeks, while rats in the control group were administered with tap water. Then the rats were killed at 8, 16, 20, 24, 28 weeks and their tongues were removed for general observation, histological assessment and HSF1 immunohistochemical staining. Results：Gross changes were observed, including granulations, white patches, verruca, cauliflower-like shape leukoplakia and ulcer-like changes on the posterior part of the tongue dorsum of experimental group with increasing concentrations and prolonged action of 4NQO. Their corresponding histopathological results ranged from hyperplasia, mild dysplasia (MiDP), moderate dysplasia (MoDP) and severe dysplasia(SDP), in situ carcinoma (ISC) to early invasive carcinoma (EIC). The incidence of tongue cancer in rats treated with 4NQO for 8, 16, 20, 24, 28 weeks was 0, 20.0%, 50.0%, 66.70% and 100%. Rat tongue mucosa epithelium of the control rats was almost negative or low for HSF1 staining. But with the aggravation of the tongue mucosal dysplasia, the positive of HSF1 of the experimental rats increased obviously. HSF1 was distributed throughout the entire cancer nest in carcinoma in situ. The of HSF1 was low in cancer epithelium of well-differentiated squamous cell carcinoma, while high in carcinoma stromal fibroblasts. Conclusions：4NQO drinking water can induce rat tongue carcinogenesis, wich helps to successfully establish the rat tongue carcinogenesis model and HSF1 may play a key role in the development of the cancer.

李传祝王飞王琼刘来奎. 4NQO诱导大鼠舌黏膜癌变过程中HSF1的表达及意义[J]. , 2016, 7(3): 129-133.

参考文献

[1]Jemal A, Bray F, Center MM, et al.Global cancer statistics[J].CA Cancer J Clin, 2011, 61(2):69-90
[2]Li H, Zhang J, Chen SW，et al.Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer[J].J Transl Med, 2015, 13:198-
[3]Tanaka T, Kohno H, Sakata K, et al.Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis[J].Carcinogenesis, 2002, 23(8):1361-1367
[4]Scherz-Shouval R, ?Santagata S, ?Mendillo ML, et al.The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy[J].Cell, 2014, 158(3):564-578
[5]Jiang S, Tu K, Fu Q, et al.Multifaceted roles of HSF1 in cancer[J].Tumour Biol, 2015, 36(7):4923-4931
[6]Sugimura T, Terada M, Yokota J, et al.Multiple genetic alterations in human carcinogenesis[J].Environ Health Perspect, 1992, 98:5-12
[7]Lee CC, Ho HC,Su YC,et al.Comparison of different comorbidity measures for oral cancer patients with surgical intervention: A longitudinal study from a single cancer center[J].Auris Nasus Larynx, 2016, 43(3):322-329
[8]Dayan D, Hirshberg A, Kaplan I, et al.Experimental tongue cancer in desalivated rats[J].Oral Oncol, 1997, 33(2):105-109
[9]Mikita H, Tanaka T, Fujitsuka H, et al.Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin[J].Cancer Res, 1996, 56(21):4904-4909
[10].Res, 1996, 56(21):4904-9
[11]马琴, 王斌全, 温树信, 等.4NQO饮水法诱发小鼠头颈部鳞状细胞癌模型的建立[J].中国耳鼻咽喉头颈外科, 2009, 16(9):490-493
[12]Hoang AT, Huang J, Rudra-Ganguly N, et al.A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma[J].Am J Pathol, 2000, 156(3):857-864
[13]Tang D, Khaleque MA, Jones EL, et al.Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo[J].Cell Stress Chaperones, 2005, 10(1):46-58