Abstract
Altered cyclin-dependent kinase activity is observed in many human malignancies. Cyclin-dependent kinases that promote cell cycle progression may be promising targets in the treatment of cancer. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for medullary thyroid cancer were investigated in the present study. Roniciclib inhibited medullary thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib induced caspase-3 activity and contributed to apoptosis. Cell cycle progression was arrested in the G2 phase. In vivo, roniciclib treatment retarded the growth of tumors of medullary thyroid cancer xenografts. In addition, roniciclib in combination with sorafenib was more effective than either single treatment in a xenograft model. No morbidity was observed in animals treated with single roniciclib therapy and combination treatment of roniciclib and sorafenib. These data provide a rationale for clinical assessment of using roniciclib in the treatment of patients with medullary thyroid cancer.
Highlights
Thyroid cancer is the most common malignancy of the endocrine system, with an increasing incidence worldwide in the past few decades [1, 2]
TT cells had lower Dm (9.6 ± 0.3 nmol/L) than that of DRO81-1 cells (16.8 ± 0.2 nmol/L). These cytotoxic effects of roniciclib in two Medullary thyroid cancer (MTC) cell lines were validated by counting viable cells using a microscope after a 4-day therapy (Supplementary Figure 1)
We evaluated the effects of roniciclib on apoptosis in two MTC cell lines
Summary
Thyroid cancer is the most common malignancy of the endocrine system, with an increasing incidence worldwide in the past few decades [1, 2]. The clinical course of MTC can be indolent for years. Aggressive MTC is associated with a high mortality rate [7]. Two multi-kinase inhibitors, cabozantinib and vandetanib, improve progression-free survival and have recently been approved by the U.S Food and Drug Administration for the treatment of progressive MTC [8, 9]. Both drugs have limited therapeutic efficacy in many patients and are associated with toxic effects that usually lead to interruption of treatment.
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