BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments
BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments
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DOI：
10.1097/cad.0000000000000157
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发表时间：
2015-01-01
影响因子：
2.3
通讯作者：
Brassesco, Maria S.
中科院分区：
文献类型：
--
作者：
Bogado, Rodrigo F. E.;Pezuk, Julia A.;Brassesco, Maria S.
polo样激酶1 （PLK1）是有丝分裂的关键调节因子，在儿童癌症中经常过度表达，并与不良预后相关。先前的报道表明，抑制PLK1可能是一种很有希望的骨肉瘤抗癌治疗方法。在这项研究中，我们在HOS和MG-63细胞系中测试了第二代PLK1抑制剂BI 6727和GSK461364，无论是单独使用还是与甲氨蝶呤、顺铂、长春花碱、阿霉素或电离辐射联合使用。两种PLK1抑制剂在细胞生长抑制、细胞凋亡诱导和放射增敏方面的作用相同。然而，BI 6727或GSK461364与常规药物联合使用，体外抗肿瘤增效作用微不足道。我们的研究结果加强了PLK1抑制剂在骨肉瘤药物干预中的潜在应用，尽管它们在多化疗方案中的适用性有待进一步研究。抗癌药物26:56-63 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins。
Polo-like kinase 1 (PLK1), a key regulator of mitosis, is often overexpressed in childhood cancers and is associated with poor prognosis. Previous reports have shown that inhibition of PLK1 might serve as a promising anticancer treatment for osteosarcoma. In this study, we tested the second-generation PLK1 inhibitors BI 6727 and GSK461364 in HOS and MG-63 cell lines, both as a single agent and in combination with methotrexate, cisplatin, vinblastine, doxorubicin, or ionizing radiation. Both PLK1 inhibitors worked equally in terms of cell growth arrest, apoptosis induction, and radiosensitization. Combining BI 6727 or GSK461364 with conventional treatments, however, showed trivial synergistic antitumor effects in vitro. Our results reinforce the potential use of PLK1 inhibitors for a pharmacologic intervention in osteosarcoma, although their applicability in polychemotherapeutic regimens deserves further investigation. Anti-Cancer Drugs 26: 56-63 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.