非诺贝特对人肺癌裸鼠移植瘤生长及PPARα、Bcl-2、NF-κB表达的影响  被引量:2

Inhibitory of Fenofibrate on the growth of human lung cancer xenograft in nude mice and the effect on the expressions of PPARα, Bcl-2,NF-κB

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作  者:王绩英[1] 曾锦荣[1] 王昌明[1] 莫碧文[1] 刘春妮[1] 王涛[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:《中国老年学杂志》2013年第20期5035-5037,共3页Chinese Journal of Gerontology

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2011008)

摘  要:目的探讨过氧化物酶体增殖因子激活受体(PPARα)激动剂非诺贝特与顺铂联用对人肺癌A549细胞裸鼠移植瘤生长抑制和凋亡的影响。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生理盐水对照组(A组),非诺贝特200 mg/kg组(B组),顺铂2 mg/kg组(C组),非诺贝特200 mg/kg+顺铂2 mg/kg(D组),接种2 w后开始给药,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 w,描绘肿瘤生长曲线,于最后一次给药后48 h脱颈白处死各组裸鼠,剥离皮下移植瘤;Western印迹检测各组移植瘤PPARα、NF-κB蛋白的表达;免疫组化SP法检测移植瘤组织中抗凋亡蛋白Bcl-2的表达。结果 Western印迹结果示D组较B、C组,PPARα蛋白表达升高、NF-κB蛋白表达降低(P<0.05);免疫组化结果显示D组与单用药组相比移植瘤中Bcl-2的表达下调(P<0.05)。结论非诺贝特、顺铂具有抑制人肺癌A549裸鼠移植瘤的生长作用,其可能机制是通过激活PPARα途径下调NF-κB、Bcl-2蛋白的表达从而起到抗肿瘤的作用。Objective To investigate the inhibitory and apoptosis effect on peroxisome proliferator activated receptor alpha (PPARα) agonist Fenofibrate combination with cisplatin(DDP) on growth of A549 cell line xenograft in nude mice.Methods The human lung cancer xenograft mode in nude mice was established in A549 cell.Twenty four Balb/c-nu mice with lung cancer xenograft were randomly divided into:① control (A group,NS 0.2 ml) ; ② Fenofibrate 200 mg/kg (B group) ; ③ DDP 2 mg/kg (C group) ; ④ Fenofibrate 200 mg/kg + DDP 2 mg/kg (D group) groups.DDP was given by intraperitoneal injection every two days and Fenofibrate was intragastrically administered every day.Different treatments were served for 3 weeks after fourteen days.The curves of BALB/c-nude mice growth were drawn,all the BALB/c-nude mice were killed at 48 h after the last dose,subcutaneous tumors were peeled off.Expressions of PPARα,Bcl-2,NF-кB protein in subcutaneous tumors were determined by immunohistoehemical method or Western blot method.Results Western blot results showed PPARα protein expression of D group was higher than that of B,C groups and NF-кB protein expression was lower than that of B,C groups.Immunohistochemistry showed that Bcl-2 expression of D group was significantly lower than that of B,C groups.Conclusions Fenofibrate could inhibit and enhance inhibition of the growth of xenograft tumor in combination with DDP.The possible mechanism is through the activation of PPARα signaling pathway and downregulating expression of NF-кB,Bcl-2 protein.

关 键 词:肺恶性肿瘤 非诺贝特 PPARΑ BCL-2 NF-ΚB 

分 类 号:R734.2[医药卫生—肿瘤]

 

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