大豆异黄酮诱导裸鼠人胃癌移植瘤凋亡(英文)  

The anticancer activity of genistein on implanted tumor of human primary gastric carcinoma cells in nude mice

作　　者：周海波[1] 蔡建庭[1] 杜勤[1] 陈金明[1] 

机构地区：[1]浙江大学附属二院消化科,浙江杭州31009

出　　处：《中国病理生理杂志》2007年第12期2379-2384,共6页Chinese Journal of Pathophysiology

摘　　要：目的:探讨大豆异黄酮诱导人胃癌原代细胞裸鼠移植瘤凋亡的机制。方法:建立人胃癌原代细胞裸鼠移植瘤模型并测定移植瘤的生长曲线;25只BALB/C裸鼠接种胃癌原代细胞悬液生成移植瘤后,不同剂量的大豆异黄酮进行瘤旁注射,透射电镜和TUNEL法检测肿瘤组织细胞凋亡情况,免疫组化法和RT-PCR法检测肿瘤组织的凋亡相关基因bcl-2和bax的表达情况。结果:大豆异黄酮对胃癌原代细胞移植瘤有明显的抑制作用,在剂量为0.5 mg/kg、1 mg/kg、1.5 mg/kg时,其抑制率分别为10.6%、29.7%和39.1%;透射电镜发现大豆异黄酮导致移植瘤内大量细胞发生调亡;TUNEL染色法发现大豆异黄酮注射组瘤细胞的凋亡指数是随剂量递增(28.7%±1.1%、33.4%±1.4%和37.1%±1.0%)。免疫组织化学法发现大豆异黄酮注射组的Bcl -2蛋白阳性细胞率随剂量递减(11.8%±0.9%、5.7%±0.8%和4.0%±0.8%),而Bax蛋白阳性细胞率随剂量递增(20.0%±±1.2%、24.7%±0.9%和29.3%±1.6%);RT-PCR法发现,大豆异黄酮注射组的bcl -2mRNA条带强度随剂量的增大而递减,并明显低于对照组(P<0.05);而baxmRNA条带强度递增,并明显低于对照组(P<0.05),而2对照组bcl -2,bax之间差异无统计学意义(P>0.05)。结论:大豆异黄酮对胃癌原代细胞移植瘤有明显的抑制作用,通过下调bcl -2的表达和上调bax的表达而诱导胃癌裸鼠移植瘤细胞发生凋亡,是其抗胃癌作用的机制之一。AIM ： To investigate the apoptosis of implanted tumor of primary human gastric cancer cells in nude mice induced by genistein and the relation between this apoptosis and expression of bcl - 2 and bax. METHODS： Establishing a transplanted tumor model by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. The different doses of genistein （0.5mg/kg, lmg/kg and 1.5 mg/kg ） were directly injected beside tumor body respectively, for six times at an interval of two days. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alteration by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis - regulated gene bcl - 2 and bax by immunohistochemical staining and RT -PCR. RESULTS： Genistein could significantly inhibit carcinoma growth when it was injected near the carcinoma. Genistein induced implanted tumors cells to undergo apoptosis with apoptotic characteristics by transmission electron microscope. The apoptosis index of above three groups was increased progressively. Positive rate of Bcl - 2 protein of above three groups was decreased progressively and positive rate of Bax protein of above three groups was increased pro- gressively by immunohistochemical staining. The density of bcl -2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT - PCR. CONCLUSION： Genistein is able to induce the apoptosis of transplanted tumor cells. This apoptosis may be mediated by down - regulating bcl - 2 and up - regulating bax mRNA and its protein.

关 键 词：染料木黄酮 小鼠 裸 细胞凋亡 胃肿瘤 

分 类 号：R363[医药卫生—病理学]