一种新型透明细胞卵巢癌患者来源细胞系的药物筛选和激酶活性分析

Rei Noguchi, Yuki Yoshimatsu, Akane Sei, H. Yoshida, Tomoyasu Katou, T. Kondo
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引用次数: 1

摘要

透明细胞癌(CCC)是一种罕见的卵巢癌亚型,对标准铂类化疗耐药,导致CCC患者预后不良。激酶是抗癌药物的靶点;很少有研究通过分析激酶活性来确定激酶抑制剂作为新的抗癌药物。在这项研究中,我们旨在通过综合激酶活性测定和药物筛选来寻找治疗CCC的新型抗癌药物。利用51岁患者的腹水,我们建立并鉴定了NCC-cOV1-C1细胞系。我们筛选了152种小的抗癌化合物的抗增殖作用,并利用PamStation12平台进行了全面的激酶活性测定。NCC-cOV1-C1细胞携带HFN1β扩增拷贝数变化,并表现出恒定生长、球状形成和侵袭能力。NCC-cOV1-C1细胞对盐酸依达柔比星和伏立诺他有显著反应。激酶活性分析显示,SRC和EGFR在nc - cov1 - c1细胞中高度活化;SRC抑制剂达沙替尼和EGFR抑制剂拉帕替尼表现出抗增殖作用和下调下游信号。NCC-cOV1-C1细胞系将为CCC的基础和临床前研究提供有用的工具,盐酸依达柔比星、伏立诺他、达沙替尼、拉帕替尼的临床应用值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Drug screening and kinase activity profiling of a novel patient-derived cell line of clear cell ovarian carcinoma
Clear cell carcinoma (CCC) is a rare subtype of ovarian cancer resistant to standard platinum chemotherapy, which leads to a poor prognosis for patients with CCC. Kinases are targets for anticancer drugs; few studies have profiled kinase activity to identify kinase inhibitors as novel anticancer drugs. In this study, we aimed to identify novel anticancer drugs for the treatment of CCC with comprehensive kinase activity assay and drug screening. Using ascites from a 51-year old patient, we established and characterized the NCC-cOV1-C1 cell line. We screened the antiproliferative effects of 152 small anticancer compounds and conducted comprehensive kinase activity assays with the PamStation12 platform. The NCC-cOV1-C1 cells harbor copy number variation of HFN1β amplification, and exhibit constant growth, spheroid formation, and invasion capability. NCC-cOV1-C1 cells responded remarkably to idarubicin HCl and vorinostat. The kinase activity assay revealed that SRC and EGFR were highly activated in NCC-cOV1-C1 cells; the SRC inhibitor dasatinib and the EGFR inhibitor lapatinib exhibited antiproliferative effects and down-regulation of downstream signaling. The NCC-cOV1-C1 cell line will be a useful tool for basic and preclinical study of CCC, and the clinical utility of idarubicin HCl, vorinostat, dasatinib, lapatinib is worthy of further investigation.
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