DACARBAZINE INITIATES SIRT1-INDEPENDENT OVEREXPRESSION OF ANTI-APOPTOTIC BCL2 IN MELANOMA CELLS IN VIVO

DOI: https://doi.org/10.29296/24999490-2024-04-06

E.Z. Lapkina, V.A. Kutsenko, T.G. Ruksha
Federal State Budgetary Educational Institution of Higher Education «Prof. V.F. Voino-Yasenetsky
Krasnoyarsk State Medical University» of the Ministry of Healthcare of the Russian Federation,
P. Zeleznyak street, 1, Krasnoyarsk, 660022, Russian Federation

Introduction. Cancer cell drug resistance in melanoma is associated with evasion of apoptosis-induced stimuli. Assessing the level of expression of the BCL2 and SIRT1 genes in distant organs and the tumor node makes it possible to assess the resistance of melanoma cells to chemotherapeutic effects associated with the activation of anti-apoptotic mechanisms. The aim of the study. Relative expression level of the SIRT1 and BCL2 estimation in the tumor node and target organs for distant metastatic (lungs, liver) in B16 melanoma bearing mice under dacarbazine treatment. Methods. In the in vivo model of B16 melanoma. Intraperitoneal administration of dacarbazine was used in vivo. Subsequently, total RNA was extracted from the cells of tumor node and distant organs (liver, lungs). Relative expression levels of the apoptosis and cell proliferation genes SIRT1, BCL2 were analyzed using real-time PCR (RT-PCR) method. Results. When exposed to dacarbazine, the relative level of expression of the anti-apoptotic BCL2 in the tumor in B16 melanoma increases by 5.7-fold. The relative expression level of SIRT1 in the lungs after intraperitoneal injections of dacarbazine decreased by 3.8-fold.; in the liver of mice, the relative expression level of SIRT1 increased by 1.94-fold. The relative level of BCL2 expression in the lungs after intraperitoneal injections of dacarbazine decreased by 31-fold. In mouse liver, the relative expression level of BCL2 increased 1.94-fold. Conclusion. When exposed to dacarbazine as a damaging factor in skin melanoma in vivo, SIRT1-mediated protection against apoptosis of liver cells and SIRT1-mediated activation of apoptosis in lung tissue cells of mice can be replaced, while in the melanoma tumor cell a pattern of SIRT1-independent induction of anti-apoptotic processes by dacarbazine in B16 melanoma bearing mice under dacarbazine treatment.
Keywords: 
skin melanoma, dacarbazine, SIRT1, BCL2, drug resistance
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