Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland.
Department of Evolutionary and Physiological Ecology, Faculty of Biology, University of Bialystok, Ciolkowskiego Street 1J, 15-245 Bialystok, Poland.
Int J Mol Sci. 2024 Oct 5;25(19):10713. doi: 10.3390/ijms251910713.
There is growing evidence that the body's energy expenditures constitute a significant risk factor for the development of most deadly diseases, including cancer. Our aim was to investigate the impact of basal metabolic rate (BMR) on the growth and progression of colorectal cancer (CRC). To do so, we used a unique model consisting of three lines of laboratory mice () artificially selected for high (HBMR) and low (LBMR) basal metabolic rate and randomly bred individuals (non-selected, NSBMR). The experimental individuals were implanted with human colorectal cancer cells DLD-1. The variation in BMR between the lines allowed for testing the impact of whole-body metabolism on oxidative and antioxidant parameters in the liver throughout the cancerogenesis process. We investigated the dependence between metabolic values, reactive oxygen species (ROS) levels, and Kelch-like ECH-associated protein 1-based E3 ligase complexes () gene activity in these animals. We found that the HBMR strain had a higher concentration of oxidative enzymes compared to the LBMR and NSBMR. Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR.
越来越多的证据表明，人体的能量消耗是大多数致命疾病（包括癌症）发展的一个重要风险因素。我们的目的是研究基础代谢率（BMR）对结直肠癌（CRC）生长和进展的影响。为此，我们使用了一个独特的实验室小鼠模型，该模型由三条人工选择的具有高（HBMR）和低（LBMR）基础代谢率的线和随机繁殖的个体（非选择，NSBMR）组成。实验个体被植入人结直肠癌细胞 DLD-1。这些线之间的 BMR 变化允许测试全身代谢对整个癌变过程中肝脏中氧化和抗氧化参数的影响。我们研究了这些动物中代谢值、活性氧（ROS）水平和 Kelch 样 ECH 相关蛋白 1 基 E3 连接酶复合物（）基因活性之间的依赖性。我们发现，与 LBMR 和 NSBMR 相比，HBMR 株的氧化酶浓度更高。此外，CRC 肿瘤的生长速度与高代谢率动物中氧化应激酶水平和表达的改变有关。我们的结果表明，CRC 系 DLD-1 的更快生长和发育与高 BMR 动物中酶促氧化还原失衡有关。
