Targeting MET by Tyrosine Kinase Inhibitor Suppresses Growth and Invasion of Nasopharyngeal Carcinoma Cell Lines
Targeting MET by Tyrosine Kinase Inhibitor Suppresses Growth and Invasion of Nasopharyngeal Carcinoma Cell Lines
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DOI：
10.1007/s12253-011-9452-1
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发表时间：
2012-04-01
影响因子：
2.8
通讯作者：
Wong, Elaine Y.
中科院分区：
文献类型：
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作者：
Lau, Patrick C.;Wong, Elaine Y.
鼻咽癌（NPC）是一种在流行地区具有高侵袭性和转移性的常见癌症。现在已知HGF-MET信号通路在介导许多不同类型癌症的侵袭性生长中起重要作用，包括头颈部鳞状细胞癌。在细胞系模型中，HGF已显示出促进鼻咽癌细胞生长和侵袭的作用。本研究旨在验证小分子酪氨酸激酶抑制剂PHA665752对MET的抑制作用对鼻咽癌细胞系生长和侵袭潜能的影响。应用PHA665752处理鼻咽癌细胞株，对MET蛋白进行免疫组化，并对MET及其下游级联信号蛋白进行western blot分析。研究了PHA665752对细胞生长、迁移和侵袭的影响。PHA665752对MET的抑制作用对鼻咽癌细胞的生长、迁移和侵袭具有高度显著的抑制作用。经PHA665752处理后，鼻咽癌细胞中phospho-MET、phospho-Akt、phospho-MAPK、phospho-STAT3、cyclin D1、β -catenin和PCNA表达下调。酪氨酸激酶抑制剂抑制MET通过下调多种信号传导癌蛋白抑制鼻咽癌细胞生长和侵袭潜能。MET是鼻咽癌重要的治疗靶点，值得进一步研究和临床试验。
Nasopharyngeal carcinoma (NPC) represents a common cancer in endemic areas with high invasive and metastatic potential. It is now known that the HGF-MET signaling pathway plays an important role in mediating the invasive growth of many different types of cancer, including head and neck squamous cell carcinoma. HGF has been shown to stimulate NPC cell growth and invasion in cell line model. The current study aims at demonstrating the effect of MET inhibition by small molecule tyrosine kinase inhibitor PHA665752 on the growth and invasive potential of NPC cell lines. NPC cell lines were used for immunohistochemistry for the MET protein, as well as western blot analysis on MET together with its downstream cascade signaling proteins after treatment with PHA665752. The effect on cell growth, migration and invasion after PHA665752 treatment was also studied. MET inhibition by PHA665752 resulted in highly significant inhibition on NPC cell growth, migration and invasion in vitro. Down-regulation of phospho-MET, phospho-Akt, phospho-MAPK, phospho-STAT3, cyclin D1, beta-catenin and PCNA was detected in NPC cells after PHA665752 treatment. MET inhibition with tyrosine kinase inhibitor resulted in suppression of NPC cell growth and invasive potential via down-regulation of a variety of signaling onco-proteins. MET is an important therapeutic target for NPC that warrants further studies and clinical trials.