p38α及β亚型对胰腺癌细胞生物学行为的影响  

Functions of p38 mitogen-activated protein kinase alpha and beta in human pancreatic cancer cells

作　　者：谢学海[1] 田孝东[1] 马永簌 陈依然[1] 杨尹默[1] Xie Xuehai;Tian Xiaodong;Ma Yongsu;Chen Yiran;Yang Yinmo(Department of General Surgery, Peking University First Hospital, Beijing 100034, China)

机构地区：[1]北京大学第一医院普通外科,100034

出　　处：《中华实验外科杂志》2019年第2期261-263,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金面上项目 (81672353).

摘　　要：目的 观察p38亚型α和β对胰腺癌细胞生物学行为的影响。方法 Western blot实验检测人胰腺癌细胞株中p38α、p38β、p38γ、p38δ的表达;建立稳定转染靶向抑制p38α和p38β表达水平的细胞克隆,通过噻唑蓝(MTT)比色、克隆形成实验、运动轨迹、细胞侵袭、裸鼠体内成瘤等实验观察p38α和p38β对胰腺癌细胞增殖、生长、侵袭以及体内成瘤能力的影响。结果 p38 4个亚型在7种胰腺癌细胞株中有不同水平表达;选择性抑制p38α后,Mia Paca-2和Panc-1细胞增殖、运动和侵袭能力显著下降,且裸鼠体内成瘤实验可见肿瘤体积显著增加。选择性抑制p38β后,可以观察到细胞生长和增殖变慢,但未见运动和侵袭能力的变化。体内成瘤实验中,Mia Paca-2两个下调p38β细胞克隆成瘤率分别为18.3%和50.0%,较野生型和空质粒转染组显著下降,且肿瘤体积显著减小(P<0.05);Panc-1两个下调p38β细胞克隆成瘤率为25.0%和12.5%,较野生型和空质粒转染组显著下降(P<0.05)。结论 p38在胰腺癌细胞中表达,其亚型p38α和p38β对胰腺癌Mia Paca-2和Panc-1细胞生物学行为的影响存在不同作用。Objective To elucidate possible functions of p38α and p38β in human pancreatic cancer.Methods Expression of p38α, p38β, p38γ and p38δ were determined by immunoblot in 7 cultured human pancreatic cancer cell lines. To selectively inhibit p38α or p38β, cell clones were established in a stable manner expression either p38α short hairpin RNA (shRNA) or p38β shRNA. Proliferation, single cell movement, in vitro migration, colony forming ability as well as in vivo tumorigenicity were determined by methyl thiazol tetrazolium (MTT) assay, video-time laps microscopy, boyden-chamber, soft-agar assay, tumor formation and growth in nude mice respectively.Results All pancreatic cancer cells showed p38 isoforms protein expression at various levels. Selective inhibition of p38α or p38β in Mia Paca-2 and Panc-1 cells revealed that both kinases enhance cell proliferation and anchorage-independent growth. Single cell movement and cell invasion were markedly reduced in p38α shRNA expressing clones, but not altered in p38β shRNA expressing clones. Inhibition of p38α enhanced in vivo tumorigenicity profoundly in Mia Paca-2 and Panc-1 cells. In Mia Paca-2 cell, the in vivo tumor formation rate of two p38β shRNA expressing clones is 18.3% and 50.0% respectively, which decreased significantly comparing to the wild type cell and null vector transfection cell. The tumor volume decreased significantly either (P<0.05). In Panc-1 cell, the in vivo tumor formation rate of two p38β shRNA expressing clones is 25.0% and 12.5% respectively.Conclusion p38 mitogen activated protein kinases (p38MAPKs) are expressed in pancreatic cancer cells and the isoforms may exert different functions.

关 键 词：p38丝裂酶原活化蛋白激酶 胰腺癌 p38α p38β 

分 类 号：R735.9[医药卫生—肿瘤]