In vitro targeting of Polo-like kinase 1 in bladder carcinoma : comparative effects of four potent inhibitors.
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2013
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Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has
changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities
of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder
carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments
with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented
cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences
were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of
death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with
the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic
effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate
that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and
dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical
tests are still needed to corroborate the usefulness of using them in combination with other commonly used
chemotherapeutic drugs.
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Bladder cancer, Cell lines
Citação
BRASSESCO, M. S. et al. In vitro targeting of Polo-like kinase 1 in bladder carcinoma: comparative effects of four potent inhibitors. Cancer Biology & Therapy, v. 14, p. 648–657, 2013. Disponível em:<https://www.tandfonline.com/doi/full/10.4161/cbt.25087> . Acesso em: 16 jun. 2017.