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
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篇名: 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
TITLE: Effects of irbesartan combined with 5-fluorouracil on the proliferation and ERK/PPARγ signaling pathway of Lewis lung cancer cells
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(1×10-3mmol/L)、Irb高浓度组(1×10-1mmol/L)、5-FU组(10μmol/L)、Irb低浓度+5-FU组(Irb1×10-3mmol/L+5-FU10μmol/L)和Irb高浓度+5-FU组(Irb1×10-1mmol/L+5-FU10μmol/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Westernblot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。
ABSTRACT: 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 receptor γ(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 (10 μmol/L),Irb LD+ 5-FU group (Irb 1×10-3 mmol/L+5-FU 10 μmol/L)and Irb HD+ 5-FU group (Irb 1×10-1 mmol/L+5-FU 10 μmol/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 PPAR γ protein 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 PPARγ were significantly reduced in the other five groups ,and the protein level of p 53 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/PPARγ signal pathway.
期刊: 2022年第33卷第16期
作者: 翟美娟,季士亮,江翊国,白秀华
AUTHORS: ZHAI Meijuan ,JI Shiliang ,JIANG Yiguo,BAI Xiuhua
关键字: 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
KEYWORDS: irbesartan;5-fluorouracil;lung cancer cell ;
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