Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
J Biochem Mol Toxicol. 2021 Feb;35(2):e22645. doi: 10.1002/jbt.22645. Epub 2020 Oct 5.
This study was carried out to investigate the potential effects of vitamin B12 and sitagliptin, and their possible synergistic effect with doxorubicin (DOX) on the Ehrlich solid tumor model. B12, sitagliptin, and their combination with DOX were administered to tumor-bearing mice for 21 days. Treatment with B12, sitagliptin, as well as their combinations with DOX caused a significant inhibition of tumor growth and increased the survival time. Malondialdehyde levels and the relative expression of tumor necrosis factor-α and nuclear factor kappa B were significantly decreased, whereas the total antioxidant capacity was significantly increased in all treated groups, except the DOX-treated one, when compared with the positive control group. Moreover, increased apoptosis was also observed by increased cleaved caspase-3 immunostaining and histopathological examination. In conclusion, the antitumor activity of B12 and sitagliptin could be attributed to their ability to induce apoptosis and suppress oxidative stress and inflammation.
本研究旨在探讨维生素 B12 和西他列汀，以及它们与阿霉素（DOX）联合应用对艾氏腹水瘤模型的潜在影响。B12、西他列汀及其与 DOX 的联合用药在荷瘤小鼠中连续给药 21 天。B12、西他列汀以及它们与 DOX 的联合用药均显著抑制肿瘤生长并延长了生存时间。与阳性对照组相比，除 DOX 组外，所有治疗组的丙二醛水平和肿瘤坏死因子-α 和核因子 kappa B 的相对表达均显著降低，而总抗氧化能力显著升高。免疫组化检测和组织病理学检查发现，凋亡也有所增加。综上所述，B12 和西他列汀的抗肿瘤活性可能归因于其诱导凋亡以及抑制氧化应激和炎症的能力。
