GW2974对实验性口腔癌中EGFR及其相关原癌基因的抑制作用  

Inhibitng effects of GW2974 on EGFR and proto-oncogenes in DMBA-induced hamster buccal pouch carcinogenesis model

作　　者：李萍[1] 葛化冰[1] 孙正[1] 

机构地区：[1]首都医科大学口腔医学院牙周黏膜科

出　　处：《北京口腔医学》2008年第2期61-64,共4页Beijing Journal of Stomatology

基　　金：北京市2006年自然科学基金资助项目(编号:7062027)

摘　　要：目的观察小分子酪氨酸激酶抑制剂GW2974对实验性口腔癌中EGFR的表达及其相关原癌基因c-Fos、c-Jun的抑制作用。方法90只金黄地鼠于左侧颊囊涂0·5%DMBA,每周3次。6周后随机分为阳性对照组、GW2974低浓度组、GW2974高浓度组。阳性对照组不做处理,其余两组于左侧颊囊涂抹不同浓度的GW2974(4mM/L,8mM/L)。24周末处死所有动物,取左侧颊囊黏膜,光镜下观察各组癌数目,并用免疫组化方法检测各组实验标本中EGFR及c-Fos、c-Jun的表达情况。结果通过局部应用4mM/L和8mM/L的GW2974,鳞癌数目分别从1·83±1·91下降到0·67±0·99(P<0·05)和0·43±0·68(P<0·01)。用药后的c-Fos、c-Jun表达水平均降低,呈现一定的剂量-效应关系;而EGFR的表达未见明显变化。结论GW2974可以明显抑制实验性口腔癌中的原癌基因c-Fos、c-Jun的表达,但对EGFR的表达影响不大,推测GW2974可能是通过阻断原癌基因c-Fos、c-Jun参与的细胞增殖和信号传导通路来达到抑制口腔癌发生的。Objective To study the inhibiting effects of GW2974, a tyrosine kinase inhibitors （TKIs）, on EGFR and proto-oncogenes c-Fos and c-Jun in DMBA-induced Syrian golden hamster buccal pouch carcinogenesis model. Methods A total of 90 hamsters were painted with 0. 5% DMBA in the left buccal pouches three times a week for 6 weeks, which were then divided into 3 groups： low-concentration, high-concentration and positive control groups. Positive control group received no further treatment. Two experimental groups were topically painted with 4mM/L GW2974 and 8mM/L GW2974 three times a week, respectively. Tissue samples of the left cheek pouch were obtained at the 24th week. The various expression of EGFR, c-Fos and c-Jun in specimens were detected by immunohistochemical staining and the number of tumors was counted under optical microscope, respectively. Results After topical application of GW2974 （4mM/l and 8mM/l）, the number of tumors declined from 1.83 ± 1.91 to 0. 67 ±0. 99（P 〈0. 05） and 0. 43 ±0. 68（P 〈 0. 01 ）. The expression of c-Fos and c-Jun was down-regnlated significantly in a dose-dependent manner（ P 〈 0. 05）, but there was no significant difference in the expression of EGFR. Conclusion Topical application of GW2974 can inhibit the expression c-Fos and c-Jun in an oral cancer model, but not the EGFR. The inhibiting effects of GW2974 on tumor cell proliferation and oral cancinogenesis may be realized by interfering in the downstream signaling pathway of EGFR via c-Fos and c-Jun.

关 键 词：口腔癌 表皮生长因子受体 地鼠颊囊癌发生 原癌基因 酪氨酸激酶抑制剂 

分 类 号：R739.8[医药卫生—肿瘤]