State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, Shatin, Hong Kong SAR, China.
Pathol Oncol Res. 2012 Apr;18(2):357-63. doi: 10.1007/s12253-011-9452-1. Epub 2011 Aug 25.
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, β-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.
鼻咽癌（NPC）是在高发地区常见的癌症，具有很强的侵袭性和转移性。现在已经知道，HGF-MET 信号通路在介导多种不同类型癌症的侵袭性生长中起着重要作用，包括头颈部鳞状细胞癌。已经表明 HGF 可刺激 NPC 细胞在细胞系模型中生长和侵袭。本研究旨在证明小分子酪氨酸激酶抑制剂 PHA665752 对 NPC 细胞系的生长和侵袭潜能的 MET 抑制作用。使用 NPC 细胞系进行 MET 蛋白的免疫组织化学染色，以及用 PHA665752 处理后 MET 及其下游级联信号蛋白的 Western blot 分析。还研究了 PHA665752 处理后对细胞生长、迁移和侵袭的影响。PHA665752 对 MET 的抑制导致 NPC 细胞在体外的生长、迁移和侵袭显著抑制。在用 PHA665752 处理后，NPC 细胞中检测到磷酸化-MET、磷酸化-Akt、磷酸化-MAPK、磷酸化-STAT3、细胞周期蛋白 D1、β-连环蛋白和 PCNA 的下调。酪氨酸激酶抑制剂对 MET 的抑制通过下调多种信号致癌蛋白，抑制 NPC 细胞的生长和侵袭潜能。MET 是 NPC 的一个重要治疗靶点，值得进一步研究和临床试验。
