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目的评价表皮生长因子受体酪氨酸激酶抑制剂 GW2974对由二甲基苯并蒽(dimethyl-benzanthracene,DMBA)诱导的金黄地鼠颊囊癌发生模型的抑制作用。方法 100只金黄地鼠,10只为阴性对照,其余90只于左侧颊囊涂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不同浓度的(4 mmol/L,8 mmol/L)GW2974。24周末处死所有动物,取左侧颊囊黏膜,计算肿瘤发生率、平均肿瘤数目、肿瘤体积和肿瘤负荷,光镜下观察各组单纯增生、异常增生和鳞癌数目并计算鳞癌的发生率。结果通过局部应用4 mmol/L 和8 mmol/L的 GW2974,肿瘤发生率从80.0%分别下降到43.3%(13/30,P<0.01)和36.7%(11/30,P<0.01),平均肿瘤数目从1.00±0.87分别下降到0.57±0.82(P<0.05)和0.43±0.63(P<0.05),平均肿瘤体积和平均肿瘤负荷均逐渐降低,口腔鳞状细胞癌发生率分别从70.0%下降到40.0%(12/30,P<0.05)和33.3%(10/30,P<0.01),口腔鳞状细胞癌数目分别从1.83±1.91下降到0.67±0.99(P<0.05)和0.43±0.68(P<0.01)。结论局部应用GW2974可明显抑制金黄地鼠颊囊癌的发生,提示 GW2974对口腔癌可能具有较强的癌症化学预防和治疗作用,口腔黏膜局部用药可能是预防和治疗口腔癌的一个有效途径。
Objective To evaluate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor GW2974 on the development of hamster cheek pouch carcinogenesis induced by dimethyl-benzanthracene (DMBA). Methods 100 golden hamsters, 10 negative control, and the remaining 90 were coated with 0.5% DMBA on the left cheek pouch three times a week. Six weeks later, they were randomly divided into positive control group, GW2974 low concentration group and GW2974 high concentration group. The other two groups were sacrificed on the left cheek pouch with different concentrations (4 mmol / L, 8 mmol / L) of GW2974.24 for 24 weeks. The left cheek pouch mucosa was sacrificed and the incidence of tumor was calculated. The average number of tumors, tumor volume and tumor burden were observed by light microscopy in each group of simple hyperplasia, dysplasia and squamous cell carcinoma number and calculate the incidence of squamous cell carcinoma. Results The tumor incidence decreased from 80.0% to 43.3% (13/30, P <0.01) and 36.7% (11/30, P <0.01) by topical application of 4 mmol / L and 8 mmol / The number of tumors decreased from 1.00 ± 0.87 to 0.57 ± 0.82 (P <0.05) and 0.43 ± 0.63 (P <0.05) respectively. The mean tumor volume and average tumor burden decreased gradually, and the incidence of oral squamous cell carcinoma decreased from 70.0% To 40.0% (12/30, P <0.05) and 33.3% (10/30, P <0.01) respectively. The numbers of oral squamous cell carcinoma decreased from 1.83 ± 1.91 to 0.67 ± 0.99 (P <0.05) and 0.43 ± 0.68 (P <0.01). Conclusion Topical application of GW2974 can significantly inhibit the occurrence of cheek pouch cancer in golden hamster, suggesting that GW2974 may have a strong chemoprevention and therapeutic effect on cancer of the oral cavity. Topical application of oral mucosa may be an effective way to prevent and treat oral cancer.