CDK4 expression in chordoma: A potential therapeutic target

被引:20
|
作者
Liu, Tang [1 ,2 ]
Shen, Jacson K. [1 ]
Choy, Edwin [1 ]
Zhang, Yu [1 ,3 ]
Mankin, Henry J. [1 ]
Hornicek, Francis J. [1 ]
Duan, Zhenfeng [1 ]
机构
[1] Univ Calif Los Angeles, Orthopaed Surg, Sarcoma Biol Lab, 615 Charles E Young Dr South,Biomed Sci Res Bldg, Los Angeles, CA 90095 USA
[2] Cent S Univ, Dept Orthopaed, Xiangya Hosp 2, 139 Renmin Rd, Changsha 410011, Hunan, Peoples R China
[3] Liu Hua Qiao Hosp, Dept Orthoped Surg, Guangzhou 510010, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
chordoma; p16(INK4A); CDK4; CDK6; palbociclib; DEPENDENT KINASE 4/6; CELL-CYCLE PROGRESSION; DEDIFFERENTIATED LIPOSARCOMA; INHIBITOR PALBOCICLIB; CANCER; SARCOMA; PATHWAY; SENSITIVITY; SURVIVAL; PHASE-2;
D O I
10.1002/jor.23819
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Chordomas are rare bone tumors and treatment is commonly based on a combination of surgery and radiotherapy. There is no standard chemotherapy treatment for chordoma. The aim of this study was to determine the expression of cyclin-dependent kinase 4 (CDK4) in chordoma and its therapeutic implications. We evaluated CDK4 expression both in chordoma cell lines and in chordoma tissues. Also, we investigated the functional roles of CDK4 in chordoma cell growth and proliferation. Furthermore, the therapeutic implications of targeting CDK4 in chordoma were evaluated. We found CDK4 highly expressed in chordoma cell lines and in a majority (97.7%) of chordoma tissues. Higher CDK4 expression correlated with metastasis and recurrence of chordoma. Treatment of chordoma cells using CDK4 inhibitor palbociclib could efficiently inhibit chordoma cells growth and proliferation. These data demonstrate that targeting CDK4 may be useful as a novel strategy in the treatment of chordoma. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1581-1589, 2018.
引用
收藏
页码:1581 / 1589
页数:9
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