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Background: Cellular senescence is a stress response, triggered by various stimuli such as chemotherapy treatment and causes G0/G1 cell cycle arrest followed by the production of a senescence associated secretory phenotype (SASP). p53 considered to be a modulator of these events although the precise mechanisms of it remains not clear. Aims: To determine the non-apoptotic functions of the p53 protein - the formation of the SASP phenotype of melanoma cells under the treatment of the cytostatic agent dacarbazine. Materials and methods: The study was conducted on BRO and SK-MEL-2 skin melanoma cell lines. Melanoma cells were were treated by cytostatic agent dacarbazine. Then immunocytochemical study was performed to determine the proportion of G0-positive cells and the expression of the tumor suppressor protein p53. A bioinformatic analysis was accomplished to identify for p53 regulators with determining of miR-155-5p levels in exosomes released by dacarbazine-treated melanoma cells. Results: The cytostatic drug dacarbazine increases the proportion of cells residing in the G0 phase of the cell cycle. Onco-microRNA miR-155-5p was expressed in the exosomes of the two studied cell lines BRO and SK-MEL-2 of skin melanoma. Changes in the expression level of p53 correlate with changes in miR-155-5p microRNA expression. The absence of changes in p53 expression in BRO melanoma cells may be due to the absence of changes in miR-155-5p expression levels. In the BRO cell line, no changes in the expression of the oncosuppressor p53 were observed with an increased percentage of G0-positive cells, which may be associated with the activation of other mechanisms of cell cycle arrest in the G0/G1 phase. Conclusions: Heterogeneous effect of the cytostatic agent dacarbazine on melanoma cells was revealed. For the SK-MEL-2 cell line, dacarbazine induces the release of senescence associated secretory phenotype by inhibiting exosomal production of miR-155-5p, which activates the p53 oncosuppressor, which was not observed in the BRO line. In this regard, there is a need for a more personalized approach to the treatment of malignant neoplasms.

Ruksha T., Dashkova D., Esimbekova A., Kotova K.
Russian Journal of Oncology.
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The role of mitochondria in the development of breast cancer

Tikhonov D.G., Vinokurov M.M., Kipriyanova N.S., Golubenko M.V.
Russian Journal of Oncology.
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