Pushkarov V. Taxanes effect upon cell cycle regulation in anaplastic thyroid carcinoma

Object of research: anaplastic thyroid carcinoma. Aim of study: to study taxanes effect upon cell cycle regulatory mechanisms in certain anaplastic thyroid carcinoma cell lines. To establish a link between taxanes-induced cell cycle arrest and taxanes-induced apoptosis. Methods of study and equipment: biochemical, molecular-biological, statistical analysis methods; flow cytometer FACSCalibur, centrifuge "Mikro 22R", spectrophotometer "Nanodrop", gamma-irradiation device "Pony". Theoretical and practical results: mechanisms of paclitaxel effect upon cell cycle regulatory and apoptotic factors in anaplastic thyroid carcinoma were ascertained. Paclitaxel and ionizing radiation interaction towards cell cycle apoptotic and regulatory factors in anaplastic thyroid carcinoma was studied. Data acquired provides the picture of paclitaxel mechanism of action in tumor cells. Paclitaxel effect data may serve as basis for research of new approaches in thyroid tumors treatment. Novelty: paclitaxel cytotoxicity was shown to increase in enriched medium. It was established for the first time that activation of cyclin-dependent kinases is a key link between paclitaxel-induced cell cycle arrest and paclitaxel-induced apoptosis in anaplastic thyroid carcinoma cells. It was found that in the process of paclitaxel-initiated apoptosis proteinkinases mTOR and GSK-3beta are involved. It was shown that Ras/PI3K/Akt signalling cascade inhibition leads to taxanes toxicity potentiation in anaplastic thyroid carcinoma cells. Degree of implementation: Combined effect of paclitaxel and cyclin-dependant kinases specific inhibitor roscovitine proves to be a promising strategy for further preclinical trials. Field of use: endocrinology.