Ukr.Biochem.J. 2013; Volume 85, Issue 1, Jan-Feb, pp. 51-61


Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells

V. M. Pushkarev, O. I. Kovzun, V. V. Pushkarev, M. D. Tronko

State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;

The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), γ-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). IR activated common DNA damage-induced signaling and manifested certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There was clear antagonism between Ptx and IR relative to cell cycle regulators – tumor suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but combined action of both agents enhanced caspase-3 and, especially, caspase-8 activation. The Ptx at low (1-25 nM) concentrations caused noticeable radioprotective effect.
Thus, in ATC cells the ionizing radiation and Ptx exhibited competitive effects upon phosphorylation of cell cycle controllers: p53, pRb, CHK2, cAbl and expression of Вах. At the same time, the combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases activation and survivin expression. The net effect of these events during the first 48-72 h of cells incubation can be considered as antiapoptotic – Ptx attenuated cytotoxic effect of IR.

Keywords: , , , ,


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