厄贝沙坦联合5-氟尿嘧啶对Lewis肺癌细胞增殖及ERK/PPARγ信号通路的影响  

Effects of irbesartan combined with 5-fluorouracil on the proliferation and ERK/PPARγ signaling pathway of Lewis lung cancer cells

作　　者：翟美娟[1] 季士亮 江翊国 白秀华 ZHAI Meijuan;JI Shiliang;JIANG Yiguo;BAI Xiuhua(Dept.of Pharmacy,the Affiliated Suzhou Hospitalof Nanjing Medical University/Suzhou Municipal Hospital,Jiangsu Suzhou 215002,China;Dept.of Respiratory Medicine,Suzhou Science&Technology Town Hospital,Jiangsu Suzhou 215000,China)

机构地区：[1]南京医科大学附属苏州医院/苏州市立医院药学部,江苏苏州215002 [2]苏州科技城医院呼吸科,江苏苏州215000

出　　处：《中国药房》2022年第16期1986-1989,共4页China Pharmacy

基　　金：江苏省中医药科技发展计划项目(No.YB2020064);苏州高新区卫生人才青年拔尖类项目(No.2021-01)。

摘　　要：目的探究厄贝沙坦(Irb)联合5-氟尿嘧啶(5-FU)对Lewis肺癌细胞增殖及细胞外信号调节激酶(ERK)/过氧化物酶体增殖物激活受体γ(PPARγ)信号通路的影响。方法将小鼠Lewis肺癌细胞分为正常对照组、Irb低浓度组(1×10^(-3)mmol/L)、Irb高浓度组(1×10^(-1) mmol/L)、5-FU组(10μmol/L)、Irb低浓度+5-FU组(Irb 1×10^(-3)mmol/L+5-FU 10μmol/L)和Irb高浓度+5-FU组(Irb 1×10^(-1) mmol/L+5-FU 10μmol/L),采用MTT法检测各组细胞的增殖活力;采用平板集落形成实验检测细胞集落形成数;采用Western blot法检测各组增殖细胞核抗原(PCNA)、p53、ERK1/2、磷酸化(p)-ERK1/2及PPARγ蛋白的表达水平。结果与正常对照组比较,其余5组细胞增殖活力、细胞集落形成数以及PCNA、p-ERK1/2、PPARγ蛋白表达水平均显著降低/减少(P<0.05),p53蛋白表达水平均显著升高(P<0.05),ERK1/2蛋白表达水平无明显差异(P>0.05)。Irb低浓度+5-FU组和Irb高浓度+5-FU组上述指标变化趋势均显著高于Irb低浓度组、Irb高浓度组、5-FU组(P<0.05)。结论Irb联合5-FU可抑制Lewis肺癌细胞增殖,且效果优于二者单用,其机制可能与抑制ERK/PPARγ信号通路有关。OBJECTIVE To explore the effects of irbesartan(Irb)combined with 5-fluorouracil(5-FU)on the proliferation and extracellular signal-regulated kinase(ERK)/peroxidase proliferator-activated receptorγ(PPARγ)signaling pathway of Lewis lung cancer cells.METHODS Lewis lung cancer cells from mice were divided into normal control(NC)group,Irb low-dose(LD)group(1×10^(-3)mmol/L),Irb high-dose(HD)group(1×10^(-1) mmol/L),5-FU group(10μmol/L),Irb LD+5-FU group(Irb 1×10^(-3)mmol/L+5-FU 10μmol/L)and Irb HD+5-FU group(Irb 1×10^(-1) mmol/L+5-FU 10μmol/L).MTT method was used to measure the activity of cell proliferation in each group.Plate colony formation experiment was used to determine the number of cell colonies formed in each group;Western blot method was used to detect the expression levels of proliferating cell nuclear antigen(PCNA),p53,ERK1/2,p-ERK1/2 and PPARγprotein in each group.RESULTS Compared with the NC group,the cell proliferation activity,the number of colonies formed and the protein levels of PCNA,p-ERK1/2,and PPARγwere significantly reduced in the other five groups,and the protein level of p53 was significantly increased(P<0.05);the protein expression of ERK1/2 had no significant difference(P>0.05).The changes of above indexes in Irb LD+5-FU group and Irb HD+5-FU group were more significant than Irb LD group,Irb HD group and 5-FU group(P<0.05).CONCLUSIONS Irb combined with 5-FU can inhibit the proliferation of Lewis lung cancer cell,and the effect is better than that of the two alone.The mechanism may be related to the inhibition of ERK/PPARγsignal pathway.

关 键 词：厄贝沙坦 5-氟尿嘧啶 肺癌细胞 细胞外信号调节激酶 过氧化物酶体增殖物激活受体Γ 增殖 

分 类 号：R979.1[医药卫生—药品] R361.3[医药卫生—药学]