Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells

被引:21
作者
Allegri, Lorenzo [1 ]
Baldan, Federica [1 ]
Mio, Catia [1 ]
Puppin, Cinzia [1 ]
Russo, Diego [2 ]
Krystof, Vladimir [3 ,4 ]
Damante, Giuseppe [1 ,5 ]
机构
[1] Univ Udine, Dept Med & Biol Sci, Piazzale Kolbe 4, I-33100 Udine, Italy
[2] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy
[3] Palacy Univ, Ctr Reg Hana Biotechnol & Agr Res, Lab Growth Regulators, CZ-77111 Olomuc, Czech Republic
[4] Inst Expt Bot AS CR, CZ-77111 Olomuc, Czech Republic
[5] Univ Hosp S Maria della Misericordia, Inst Med Genet, I-33100 Udine, Italy
关键词
mTOR; thyroid cancer; cell proliferation; synergy; CDK inhibitors; CARCINOMA; LINES; PATHWAYS; THERAPY;
D O I
10.3892/or.2016.4614
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Anaplastic thyroid carcinoma (ATC) is an extremely aggressive human malignancy characterized by a marked degree of invasiveness, absense of features of thyroid differentiation and resistance to current medical treatment. It is well known that ATCs are characterized by deregulation of genes related to cell cycle regulation, i.e., cyclin-dependent kinases (CDKs) and endogenous cyclin-dependent kinase inhibitors (CDKIs). Therefore, in the present study, the effect of a novel exogenous cyclin-dependent kinase inhibitor, BP-14, was investigated in three human ATC cell lines. The ATC-derived cell lines FRO, SW1736 and 8505C were treated with BP-14 alone or in combination with the mTOR inhibitor everolimus. In all ATC cell lines, treatment with BP-14 decreased cell viability and, in two of them, BP-14 modified expression of genes involved in epithelial-mesenchymal transition. Thus, our data indicate that BP-14 is a potential new compound effective against ATC. Combined treatment with BP-14 and the mTOR inhibitor everolimus had a strong synergistic effect on cell viability in all three cell lines, suggesting that the combined used of CDK and mTOR inhibitors may be a useful strategy for ATC treatment.
引用
收藏
页码:2413 / 2418
页数:6
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