过氧化物酶体增殖因子激活受体激动剂对A549细胞裸鼠移植瘤Caspase-3、Survivin表达的影响  

Inhibitory effect of peroxisome proliferator activated receptor alpha agonist on the growth of A549 cell line xenograft in nude mice and its effect on expression of Caspase-3,Survivin

作　　者：曾锦荣[1] 莫碧文[1] 王绩英[1] 刘春妮[1] 王涛[1] 陈梅晞[1] 陈峰[1] 

机构地区：[1]桂林医学院附属医院呼吸内科,广西桂林541001

出　　处：《中国药理学通报》2013年第10期1418-1422,共5页Chinese Pharmacological Bulletin

基　　金：广西壮族自治区卫生厅医疗卫生重点科研课题(No重2010046;重2012003)

摘　　要：目的观察过氧化物酶体增殖因子激活受体α(peroxisome proliferator activated receptor alpha,PPARα)激动剂非诺贝特(fenofibrate)与顺铂(cisplatin,DDP)联用对人肺癌A549细胞裸鼠移植瘤中半胱天冬蛋白酶(Caspase-3)、存活素(Survivin)表达的影响,并探讨其中机制。方法建立人肺癌A549细胞裸鼠移植瘤模型,将24只成瘤裸鼠随机分成4组:①生理盐水对照组(A组),②非诺贝特200 mg·kg-1(B组),③顺铂2 mg·kg-1(C组),④非诺贝特200 mg·kg-1+顺铂2 mg·kg-1(D组);按要求给药,顺铂采取隔天腹腔注射给药,非诺贝特采取每天灌胃给药,均连续给药3周,于最后一次给药后48 h脱颈臼处死各组裸鼠,剥离皮下移植瘤,取部分移植瘤组织置于冻存管保存于液氮中;RTPCR检测各组移植瘤组织中Caspase-3、Survivin mRNA的表达;Western blot检测Caspase-3、Survivin蛋白的表达。结果RT-PCR、Western blot结果示D组较B、C组,Caspase-3mRNA、蛋白的表达明显增强(F=400.59、F=102.08,P<0.01);Survivin mRNA、蛋白的表达明显降低(F=188.46、F=8299.94,P<0.01)。结论非诺贝特、顺铂均具有抑制人肺癌A549裸鼠移植瘤的生长作用,两药联用具有相加作用;其可能机制是通过上调凋亡蛋白Caspase-3的表达和下调Survivin的表达。Aim To investigate the effect of peroxisome proliferator activated receptor alpha （ PPARα ） agonist fenofibrate combined with cisplatin （DDP）on the growth of A549 cell line xenografi in nude mice and its mechanism. Methods The human lung cancer xeno- graft mode in nude mice was established with A549 cell. Twenty four Balb/c-nu mice with lung cancer xenograft were randomly divided into four groups： （1）con- trol group （NS 0. 2 ml） ; （2） fenofibrate 200 mg· kg^-1 group; （3）DDP 2 mg· kg^-1 group; （4）fenofibrate 200 mg· kg^-1 ＋ DDP 2 mg· kg^-1 group, administrated by groups, cisplatin was given by intraperitoneal injection every two days and fenofibrate was intragastrically ad- ministered every day. Different treatments were served for 3 weeks. All mice were sacrificed 48h after the last injection. Part of subcutaneous tumor tissue was taken into liquid nitrogen for keeping. Expression of Caspase-3, Survivin mRNA and protein in subcutane- ous tumors were determined by RT-PCR and Western blot. Results RT-PCR and Western blot results showed Caspase-3 mRNA and protein expression of D group were higher than those of B and C groups; mR- NA, protein expression of Survivin were lower than those of B and C groups. Conclusion Fenofibrate could inhibit and enhance inhibition of the growth of xenograft tumor in combination with cisplatin; the pos- sible mechanism is through increasing the expression of apoptosis protein Caspase-3 and reducing the expres- sion of Survivin.

关 键 词：肺恶性肿瘤 非诺贝特 小鼠 裸 细胞凋亡 CASPASE-3 Survivin 

分 类 号：R-332[医药卫生] R329.25