姜黄素增强胰腺癌细胞移植瘤对吉西他滨化疗敏感性的实验研究  

Curcumin potentiates the anti-tumor effects of gemcitabine in BXPC-3 pancreatic cancer xenograft model in vivo

作　　者：张洪军[1] 张兆伟[1] 刘峰[1] 曹家忠 李磊[1] 王亚征 

机构地区：[1]单县中心医院普外科,山东省274300

出　　处：《中华临床医师杂志（电子版）》2013年第21期119-121,共3页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨姜黄素增强胰腺癌BXPC-3细胞移植瘤对吉西他滨的化疗敏感性的作用及其机制。方法建立耐药胰腺癌BXPC-3细胞的裸鼠皮下移植瘤动物模型,将荷瘤鼠随机区组的方法分为:生理盐水组(Con组),吉西他滨组(Gem组,125 mg/kg),姜黄素组(Cur组,50 mg/kg),联合用药组(Gem+Cur组,吉西他滨125 mg/kg,姜黄素40 mg/kg)四组,每组8只裸鼠。各组给药均采用腹腔注射的方法,每3 d一次,共9次。实验过程中测量肿瘤体积。采用逆转录PCR检测多药耐药基因MDR1 mRNA,多药耐药相关蛋白基因MRP1 mRNA、MRP5 mRNA的表达。Western blot法及免疫组织化学法检测各组组织中P-gp、MRP1、MRP5蛋白的表达。结果末次用药1周后Gem+Cur组肿瘤体积和质量明显小于其他各组。RT-PCR结果显示Gem+Cur和Cur组MDR1、MRP1、MRP5 mRNA的表达水平明显低于Con组和Gem组。免疫组织化学染色和Western blot结果显示Cur组和Gem+Cur组的P-gp、MRP1、MRP5蛋白的表达量明显低于Con组和Gem组。结论姜黄素通过下调P-gp、MRP1、MRP5的表达量,增强胰腺癌BXPC-3细胞移植瘤对吉西他滨的化疗敏感性从而增强其抑瘤作用。Objective The objective of the present study was to investigate the effects of Curcumin on drug resistance proteins in BXPC-3 cell xenografts in mice.MethodsBXPC-3 cell xenografts were established in athymic mice, which were randomized to one of four treatment groups： group Con=0.9% sodium chloride, group Gem=125 mg/kg gemcitabine, group Cur=50 mg/kg Curcumin, and group Gem＋Cur=125 mg/kg gemcitabine＋50 mg/kg Curcumin in combination. Intraperitoneal injections were administered once every three days for a total of nine treatments. Mice were sacrificed one week following the last injection. Tumor volume and tumor weight were measured during the course of treatment. Reverse transcription polymerase chain reaction （RT-PCR） was performed to detect the expression of multidrug resistance gene 1 （MDR1）, MRP1 and MRP5 mRNA. Immunohistochemistry （IHC） and Western immunoblot（WB） analyses were performed to detect p-gp, multidrug resistance-associated proteins （MRPs） including MRP1 and MRP5 expressions.Results The combination of Gem＋Cur resulted in significantly reduced tumor volumes compared to Gem and Cur treatments alone.RT-PCR analyses showed that MDR1, MRP1 and MRP5 mRNA expression in groups Cur and Gem＋Cur were downregulated significantly compared to the other groups. IHC and WB analyses showed that p-gp, MRP1and MRP5 expression were downregulated in groups Cur and Gem＋Cur compared to the other two groups. ConclusionCurcumin potentiates the anti-tumor effects of gemcitabine in BXPC-3 cell xenografts in mice via suppression ofMDR1/P-glycoprotein and MRPs expression.

关 键 词：胰腺肿瘤 姜黄素 吉西他滨 P-GP MRPl MRP5 

分 类 号：R285.5[医药卫生—中药学]