杏丁联合吡柔比星对膀胱癌T-24细胞裸鼠移植瘤的化疗作用及机制研究  

The effects and mechanism of Xingding and THP on the T-24 bladder cancer cell xenografts in nude mice

作　　者：艾衍凯[1] 张天禹[1] 高漓[1] 覃展偶[1] 李勇平[1] 唐荣金[1] 刘升学[1] 石海林[1] 

机构地区：[1]桂林医学院附属医院泌尿外科,桂林541001

出　　处：《安徽医科大学学报》2013年第6期626-630,共5页Acta Universitatis Medicinalis Anhui

基　　金：广西省桂林市科技攻关(编号:11107009-3-2)

摘　　要：目的探讨杏丁联合吡柔比星(THP)对膀胱癌T-24细胞裸鼠移植瘤化疗疗效及其初步作用机制。方法 48只裸鼠右前肢根部背侧皮下接种人膀胱癌T-24细胞后随机分为8组:对照组、杏丁小剂量组(50 mg/kg)、中剂量组(100mg/kg)、大剂量组(150 mg/kg)、THP小剂量组(7.5 mg/kg)、常规剂量组(15 mg/kg)、A组(杏丁150 mg/kg+THP7.5 mg/kg)、B组(杏丁150 mg/kg+THP 15 mg/kg)。成瘤后第14天开始,相应各组每天给予杏丁灌胃、每3 d于肿瘤局部注射生理盐水及THP 1次,每3 d测量1次肿瘤大小,绘制移植瘤生长曲线。处理后第21天杀鼠摘取移植瘤,计算肿瘤抑制率。HE染色后光镜观察肿瘤组织病理改变,RT-PCR检测Survivin、Caspase-3基因的表达。结果与对照组比较,除杏丁小剂量组外,其余各组对移植瘤生长均有抑制作用(P<0.05)。分别与相应单用杏丁及THP组比较,A、B组对移植瘤生长抑制作用更加明显(P<0.05)。光镜结果示各用药组肿瘤标本内均出现片状坏死灶,坏死程度与药物剂量呈正相关。与相应单用THP组比较,A、B组SurvivinmRNA表达下调(P<0.05),Caspase-3 mRNA表达上调(P<0.05)。结论杏丁对移植瘤生长有抑制作用,联合THP后对移植瘤生长的抑制作用加强,其分子机制可能与抑制Sur-vivin表达进而上调Caspase-3基因表达有关。Objective To investigate the curative effect and preliminary mechanism of Xingding combined with pirarubicin （THP） on bladder cancer cell T-24 xenografts in nude mice. Methods 48 nude mice were randomly divided into 8 groups after subcutaneous injection of T-24 cell into the right legs： the control group; three Xingding groups（treated with Xingding at 150, 100 and 50 mg/kg respectively） ; two THP groups（treated with THP of routine dosage of 15 mg/kg and 7.5 mg/kg respectively） ; and two combined treatment groups （ treated with Xingding of high-dosage ＋ THP of low-dosage at 7.5 mg/kg and high-dosage ＋ THP of routine dosage at 15 mg/kg）. They were given NS or THP once every 3 days, Xingding lavage once every day, starting on the 14th day after tumorogensis. Tumor size were measured every 3 days. Animals were executed on 21 d after treatment. Light microscopy was used to observe the morphological changes. RT-PCR was used to detect Survivin and Caspase-3 mRNA expression. Results Compared to control group, proliferation inhibition on xenografts was more significant, except for Xingding of low-dosage （P 〈 0.05 ）. Proliferation inhibition on xenografts of A and B groups was more significant when given with Xingding or THP alone （P 〈 0.05 ）. Local necroses were observed in the tumor specimens by HE staining in each group except for the control group. Necrosis degree and drug dose were positively correlated. The Survivin mRNA was down-regulated after intervention whereas the Caspase-5 mRNA up-regulated after intervention in A and B groups （P 〈 0. 05 ）. Conclusion Xingding can inhibit xenografts and proliferation, combination of Xingding with THP can enhance the function of inhibition of xcnografts and proliferation. The molecular mechanism is possibly related with the suppression of the Survivin expression and the increase of the Caspase-3 gene expression.

关 键 词：杏丁 吡柔比星 SURVIVIN CASPASE-3 

分 类 号：R737.14[医药卫生—肿瘤]