乳香酸与姜黄素对二甲基苯并蒽诱导地鼠口腔癌的化学预防作用

摘要

目的 观察乳香酸和姜黄素对二甲基苯并蒽(7,12-dimethyl benzanthracene,DMBA)诱导的叙利亚金黄地鼠口腔癌的化学预防作用、两者单独和联合应用是否可以抑制口腔癌的发生及发展,并对其抗肿瘤机制进行初步探讨.方法 实验对象为160只6～8周龄、体质量80～130 g的雄性叙利亚金黄地鼠,取10只为阴性对照组,不作任何处理；其余150只金黄地鼠用0.5％ DMBA涂抹左侧颊囊6周,第7周时采用随机数字表法将地鼠分为5个用药组和1个阳性对照组(每组25只),低浓度乳香酸组、高浓度乳香酸组、低浓度姜黄素组、高浓度姜黄素组及联合用药组分别给予5、10 mg/L乳香酸溶液,5、10 μmol/L姜黄素溶液及5 mg/L乳香酸+5μmol/L姜黄素溶液涂抹地鼠左侧颊囊18周,阳性对照组不做任何处理.第25周处死全部动物,记录肉眼肿瘤发生率、肿瘤数目及体积,行HE、5-溴脱氧尿苷(5-bromodeoxyuridine,BrdU)、免疫组化染色及花生四烯酸代谢物检测.结果 肉眼可见肿瘤发生率阳性对照组为93.8％,低浓度乳香酸组80.0％,高浓度乳香酸组81.3％,低浓度姜黄素组78.3％,高浓度姜黄素组75.0％,联合用药组73.9％；各用药组平均肿瘤数目均较阳性对照组[(2.19±0.98)个]有所降低,其中高浓度姜黄素组[(1.45±0.92)个]和联合用药组[(1.13±0.81)个]显著下降(P＜0.05,P＜0.01)；各用药组组织病理学观察鳞状细胞癌病变数目均较阳性对照显著降低(P＜0.05).各用药组与阳性对照组相比均能降低BrdU增殖指数,尤以低、高浓度姜黄素组和联合用药组效果更佳(P＜0.05)；高、低浓度乳香酸组、高浓度姜黄素组及联合用药组白三烯B4含量与阳性对照组相比均显著下降(P＜0.05).结论 各用药组均可明显抑制DMBA诱导的金黄地鼠口腔癌,其中联合用药组抑癌作用效果最好,乳香酸和姜黄素可以通过降低细胞增殖活性抑制DMBA诱导的金黄地鼠口腔癌的发生、发展.%Objective To evaluate the chemopreventive effects of boswellic acid and curcumin on 7,12-dimethyl benzanthracene (DMBA)-induced oral carcinogenesis in the hamster cheek pouch model.Methods Male Syrian golden hamsters(6-8 weeks old,80-130 g in weight) were randomly divided into seven groups,with group A serving as the untreated negative control.The left cheek pouch of the remaining hamsters was topically treated with 0.5％ DMBA in mineral oil three times a week for 6 weeks.They were then randomized to six groups with group B serving as a positive control and receiving no further treatment.Groups C-G were treated topically with 5,10 mg/L boswellic acid,5,10 μ moL/L curcumin,or the combination of 5 mg/L boswellic acid and 5 μmnol/L curcumin three times per week for 18 weeks.The animals were injected with bromodeoxyuridine intraperitoneally at 50 mg/kg 2 h prior to killing.At the 25 th week all the hamsters were sacrificed and cheek pouch tissue was harvested.One half of the tissue was snap frozen in liquid nitrogen for analysis of arachidonic acid metabolites,and the other half was fixed in 10％ phosphate-buffered saline(PBS)-buffered formalin for histopathological examination.Results Six-weeks of DMBA followed by 18-weeks of topical application of boswellic acid and curcumin,both boswellic acid (5,10 mg/L) and curcumin (5,10 μmol/L) significantly inhibited the incidence from 93.8％ to 73.9％ (P＞0.05),numbers from 2.19 ± 0.98 to 1.13 ± 0.81 (P ＜ 0.01) and size of visible tumors.Microscopically the incidence of squamous cell carcinoma and BrdU index were also significantly suppressed by boswellic acid and curcumin.Conclusions Both boswellic acid and curcumin were effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model.