Comorbidity affects Вcl-2 levels in mitochondria in C57BL/6 mice with transplantable B16/F10 melanoma.

Abstract

e21581 Background: Overexpression of the Bcl-2 protein inhibits apoptosis and promotes carcinogenesis. Stress causes signaling leading to cell buffering with Bcl-2 protein above acceptable levels. The purpose of the study was to analyze the influence of comorbidity – chronic neurogenic pain (CNP) – on the Bcl-2 levels in mitochondria of cells of melanoma, the heart, skin and brain in female mice with growing tumors. Methods: Female С57ВL/6 mice were divided into groups: intact group (n = 21); control group with a CNP model – bilateral sciatic nerve ligation (n = 21); group M – B16/F10 melanoma (n = 63); CNP+M group – B16/F10 melanoma was transplanted 3 weeks after the CNP model creation (n = 63). The concentration of Bcl-2 (ng/mg of protein) was determined in mitochondrial samples by ELISA (Thermo Fisher Scientific, Austria). Statictical analysis of results: Statistica 10.0. Results: CNP decreased the Bcl-2 level in heart mitochondria by 1.3 times (p < 0.05), but increased it in skin and brain mitochondria by 5.8 and 1.3 times, respectively. Similar changes were observed in melanoma growth 1 week after its transplantation: Bcl-2 levels decreased in heart mitochondria by 1.3 times, and increased in the skin and brain by 8.9 and 1.3 times, respectively. After 2 weeks of the tumor growth, Bcl-2 in brain mitochondria decreased by 1.7 times, and it started declining in the skin by the 3rd week – by 4 times, compared to intact females. Bcl-2 in tumor mitochondria exceeded the values in the skin by more than 4 times throughout the experiment. Tumor growth in presence of CNP caused a decrease in Bcl-2 in brain mitochondria by 2.4 times after 3 weeks, and in the heart and skin – by 2 and 1.7 times, respectively, after 2 weeks. Bcl-2 in tumor mitochondria in presence of CNP was lower than in the intact skin on average by 1.8 times throughout the experiment. Conclusions: CNP as a comorbidity caused a modulating effect on the mechanisms of survival and apoptosis of cells both in the tumor and in the main organs providing the vital functions of the body - the brain and heart, and also affects the target organ of melanoma - the skin. The results demonstrated the ability of comorbidity to change levels of Bcl-2 in mitochondria depending on the stage of tumor development.