PD98059对胰腺癌Panc-1细胞株及裸鼠荷瘤增殖、凋亡的影响  

Effect of PD98059 on the proliferation and apoptosis of pancreatic cancer Panc-1 cells and tumor growth in Panc-1-xenografted nude mice

作　　者：胡益群[1] 司丽娟[1] 叶震世[1] 林振和[1] 柯细松[2] 

机构地区：[1]厦门大学附属中山医院消化内科厦门大学消化疾病研究所厦门市消化疾病中心,福建省厦门市361004 [2]挪威卑尔根大学Gade学院

出　　处：《世界华人消化杂志》2010年第26期2756-2761,共6页World Chinese Journal of Digestology

基　　金：厦门市卫生局重点基金资助项目;No.3502z20077038~~

摘　　要：目的:探讨MAPK/ERK1/2细胞信号通路在胰腺癌演化中的作用和机制.方法:用不同浓度PD98059处理Panc-1细胞及裸鼠,采用MTT法观察其对胰腺癌细胞增殖的影响,利用流式细胞仪检测胰腺癌细胞周期以及细胞凋亡的变化,使用Hoechst33258染色观察凋亡细胞的形态,应用Westernblot检测裸鼠荷瘤MAPK/ERK1/2通路P-ERK1/2蛋白的表达变化.结果:不同浓度的PD98059均可显著抑制胰腺癌Panc-1细胞的增殖(均P<0.05),且随着处理时间的延长,PD98059浓度的增加,其抑制能力逐渐增强.96h50μmol/L的PD98059抑制Panc-1细胞增殖的能力最强,其A490与对照相比具有统计学差异(0.391±0.029vs0.994±0.057,P<0.05).此时Panc-1细胞的凋亡率较对照组明显增加(11.77%±1.33%vs1.13%±0.19%,P<0.05),而20μmol/L的PD98059处理后,细胞凋亡率与对照组无明显增加.PD98059同时可以降低裸鼠荷瘤P-ERK1/2蛋白的表达,其完全抑制浓度(50μmol/L)具有最强的抑制能力.结论:MAPK/ERK1/2信号通路是调控胰腺癌细胞重要的因素之一,其作用机制与磷酸化的ERK1/2蛋白有关.AIM： To investigate the effect of PD98059, a specific inhibitor of the mitogen-activated protein kinase （MAPK）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway, on the apoptosis and proliferation of pancreatic cancer Panc-1 cells and tumor growth in Panc-1-xenografted nude mice. METHODS： After Panc-1 cells were treatedwith different doses of PD98059, cell proliferation was measured by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and apoptotic cells were examined by Hoechst 33258 staining. The expression of phosphorylated ERK1/2 in tumors in Panc-1-xenografted nude mice was detected by Western blot. RESULTS： PD98059 suppressed the proliferation of pancreatic cancer Panc-1 cells in a concen-tration- and time-dependent manner （P 0.05）. Compared with control cells, the absorbance at 490 nm （A490） was significantly lower （0.391 ± 0.029 vs 0.994 ± 0.057, P 0.05） and the apoptosis rate was significantly higher （11.77% ± 1.33% vs 1.13% ± 0.19%, P 0.05） in Panc-1 cells treated with 50 μmol/L PD98059 for 96 h. However, no significant difference was noted in the apoptosis rate between Panc-1 cells treated with 20 μmol/L PD98059 and control cells. PD98059 could restrain the expression of P-ERK1/2 proteins in tumors in Panc-1-xenografted nude mice, and the maximum inhibition was achieved with 50 μmol/L PD98059. CONCLUSION： The MAPK/ERK1/2 signaling pathway may play an important role in regulating the proliferation and apoptosis of pancreatic cancer cells.

关 键 词：PD98059 胰腺癌 MAPK/ERK1/2细胞信号通路 增殖 凋亡 裸鼠 

分 类 号：R735.9[医药卫生—肿瘤]