Asici Gamze Sevri Ekren, Kiral Funda, Bildik Aysegul, Ulutas Pinar Alkim
Department of Biochemistry, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkiye.
Vet Med (Praha). 2025 Aug 30;70(8):279-293. doi: 10.17221/24/2025-VETMED. eCollection 2025 Aug.
Osteosarcoma (OSA) is the most prevalent and aggressive malignancy of canine bones. Etoposide is an effective chemotherapeutic agent for cancer treatment, whereas ellagic acid is a naturally occurring compound with antioxidant and anticancer properties; however, both are inhibitors of the topoisomerase enzyme. In this study, the synergistic/additive effect of etoposide, known to have a growth-inhibitory impact in canine osteosarcoma (OSA) cells, and ellagic acid was investigated. The mechanism by which this effect inhibits cell growth at lower etoposide doses was also examined. The IC values of both agents were determined, and possible combination doses were generated accordingly and applied to canine OSA cells. The apoptotic effects of the combinations were evaluated based on DNA breaks and the activity levels of caspase 3, 8, and 9. These findings were supported by the expression levels of and genes as well as the AO/EtBr staining method. The effects on cell cycle and proliferation were analysed through and gene expressions. Antimetastatic effects were determined using invasion and migration assays. EA is a potential therapeutic agent for cancer treatment. In combination with ET, a higher anticancer efficacy was demonstrated compared to etoposide alone. Potential treatment side effects can be reduced by enabling the use of lower drug doses.
骨肉瘤（OSA）是犬类骨骼中最常见且侵袭性最强的恶性肿瘤。依托泊苷是一种有效的癌症化疗药物，而鞣花酸是一种具有抗氧化和抗癌特性的天然化合物；然而，二者均为拓扑异构酶抑制剂。在本研究中，对已知对犬骨肉瘤（OSA）细胞具有生长抑制作用的依托泊苷和鞣花酸的协同/相加作用进行了研究。还考察了这种作用在较低依托泊苷剂量下抑制细胞生长的机制。测定了两种药物的IC值，并据此确定了可能的联合用药剂量，并将其应用于犬OSA细胞。基于DNA断裂以及半胱天冬酶3、8和9的活性水平评估联合用药的凋亡效应。这些发现得到了 和 基因的表达水平以及AO/EtBr染色方法的支持。通过 和 基因表达分析对细胞周期和增殖的影响。使用侵袭和迁移试验确定抗转移作用。鞣花酸是一种潜在的癌症治疗药物。与依托泊苷联合使用时，与单独使用依托泊苷相比显示出更高的抗癌疗效。通过能够使用更低的药物剂量，可以降低潜在的治疗副作用。
