Calorie Restriction Decreases JAK-STAT Pathway Gene Expression, Tumor Mass and Activity of Glutathione-Dependent Enzymes

Abstract

Melanoma is one of the most aggressive types of cancer. Melanoma morbidity is increasing every year and mortality rate is high besides target therapy. Calorie restriction is lifestyle approach that can alter the activity of the pathways regulating key processes of melanomagenesis. The signaling cascades modulated by fasting includes JAK/STAT. Female С57Bl/6 mice were used for the investigation of the calorie restriction effect on the tumor growth and development. Control group is the mice on ad libitum diet, CR group is the mice on 30% calorie restricted diet. B16 melanoma cell transplantation has been carried out in the mice of the both groups after 3 months of ad libitum and CR regimes. During 15 days after melanoma cell implantation the formation of solid tumor has been occurred. Then the animals were euthanized and average mouse weight and tumor mass in both groups were evaluated. JAK/STAT gene expression was assessed by means of real-time PCR. The activity of glutathione peroxidase and glutathione-S-transferase and glutathione level were registered spectrophotometrically. 30% calorie restriction in mice with B16 melanoma decreased of tumor mass by 1.8 times (р = 0.049) as compared with the tumor mass of control group animals. STAT1 expression increased by 1.9 times, STAT3, STAT5b, STAT6, JAK1 and JAK2 expression decreased by 2.8, 3.8, 2.6, 3 and 4.5 times accordingly. Activity of glutathione peroxidase, glutathione-S-transferase and glutathione level decreased by 1.6, 3 and 1.5 times accordingly compare with control group. The received data can become pathogenical basis for the creation of new adjuvant method of anticancer therapy.