Levchuk N. Effect of paclitaxel on apoptotic and metabolic processes in tumors of the human adrenal cortex

Object of research: apoptotic and metabolic processes in the adrenal glands. Aim of study: to study the effect of paclitaxel on mechanisms that provide regulation and realization of apoptosis, as well as the main metabolic and functional processes in extratumoral and tumor tissues of human adrenal cortex. Methods of investigation and equipment: molecular-biological, biochemical and statistical methods; centrifuge "PC-6", counter LS 5000TA, spectrofluorymeter MRF - 4, centrifuge "Micro 22R", spectrophotometer-46. Theoretical and practical results: dependence of the intensity of apoptosis in extratumoral and tumor tissue of adrenal glands on the hormonal background of the organism was shown and mechanisms of paclitaxel action on apoptotic and metabolic processes in the tissue of hormonally inactive tumors were elucidated. The results provide insight on the mechanisms of paclitaxel action in the tumor tissue of human adrenal gland. Data on the effect of paclitaxel can be a basis for developing new approaches in the treatment of hormonally inactive adrenal tumors and human malignant tumors that can be originated from them by transformation. Novelty: the influence of paclitaxel on apoptosis and metabolism in extratumoral tissue and tissues of human adrenal tumors in vitro was shown. It was found that paclitaxel induced increase of intensity of the terminal stages of apoptosis - DNA fragmentation in tissue hormonally inactive adrenal tumors associated with activation of mitochondrial and postmitochondrial apoptotic processes (increased expression of Bax, activation of caspase-3, cleavage of its substrate - PARP), and mediated through p38MAРK-dependent signaling cascade. It was also shown that paclitaxel in these tissues inhibited metabolic processes, including steroidogenesis and protein synthesis. Degree of implementation: data on the effects of paclitaxel on apoptotic and metabolic processes in the tissue of hormonally inactive tumors enable us to recommend a pre-clinical tests. Field of use: endocrinology, oncology.