血根碱对人胃癌细胞GTL-16移植瘤的抑制作用及其机制探讨

Inhibitory effect of sanguinarine on growth of xenograft tumors of gastric cancer GTL-16 cells in nude mice and its related mechanism

目的:观察血根碱(sanguinarine,SAN)在动物体内的抗肿瘤作用,并初步探讨其可能的机制。方法:将人胃癌GTL-16细胞接种于BALB/c雄性裸鼠皮下,建立荷瘤动物模型;并随机分为3组,每组14只,分别用0.9%氯化钠溶液(作为对照组)、2.5和5.0 mg/kg SAN隔天灌胃7次。实验期间观察小鼠一般情况,测量肿瘤大小;28 d后处死小鼠,测量肿瘤体积并称质量;采用HE染色法对肿瘤组织进行病理学观察;蛋白质印迹法测定肿瘤组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)的表达情况。结果:SAN治疗组小鼠的肿瘤生长明显慢于对照组。用药结束时,SAN组的小鼠肿瘤体积和质量均明显小于对照组,且5.0 mg/kg SAN组的肿瘤体积和质量最小;3组之间两两比较的差异均有统计学意义(均P<0.01)。组织病理学观察发现,SAN用药显著减少了肿瘤细胞堆积和对表皮的浸润;SAN治疗组肿瘤组织中EGFR蛋白表达水平也显著低于对照组(均P<0.05)。结论:SAN可明显抑制胃癌GTL-16细胞移植瘤小鼠体内的肿瘤生长,推测这可能与下调肿瘤组织中EGFR的表达有关。

Objective： To investigate the antitumor effect of sanguinarine （SAN） in vivo and its possible mechanism. Methods： The tumor-bearing BALB/c male nude mouse models were established by subcutaneous inoculation of gastric cancer GTL-16 cells. The mouse models were divided into three groups [14 mice in each group were intragastrically administered with 0.9% NaCI solution （as the control group）, 2.5 mg/kg SAN and 5.0 mg/kg SAN every other day for 7 times, respectively]. The general status of the mice was observed, and the tumor volume was measured. After 28 days, the mice were sacrificed, then the tumor volume and weight were recorded. The histopathologic examination of tumor tissues was performed using hematoxylin-eosin （HE） staining. Then the protein expression of epidermal growth factor receptor （EGFR） in tumor tissues was detected by Western blotting. Results： As compared with the control group, the tumors grew slowly in SAN treatment groups. At autopsy, the volume and weight of tumors in SAN treatment groups were all smaller than those in the control group （P 〈 0.01）, and the tumor volume and weight were smallest in 5.0 mg/kg SAN group （P 〈 0.01）. The result of histopathologic examination revealed that SAN treatment could reduce the accumulation of tumor cells and epidermal invasion of tumor cells. The expression levels of EGFR were significantly lower in SAN treatment groups than that in the control group （P 〈 0.05）. Conclusion： SAN inhibits the growth of tumor in nude mice inoculated with gastric cancer GTL-16 cells, and which may be related to the downregulation of EGFR expression.