Wakshlag Joseph J, Balkman Cheryl A, Morgan Stewart K, McEntee Margaret C
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Am J Vet Res. 2010 Jan;71(1):89-96. doi: 10.2460/ajvr.71.1.89.
To determine the effects of the antioxidant astaxanthin on growth of canine osteosarcoma cells with and without concurrent chemotherapeutic or irradiation insult.
Cells from 3 established canine osteosarcoma cell lines (D17, OS 2.4, and HMPOS).
Growth-curve kinetics and cell cytotoxic effects were assessed by means of various treatment combinations and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was performed to examine previously identified signaling pathways that astaxanthin reportedly affects. Additionally, cell-cycle kinetic evaluations, soft agar colony-forming assays, and antioxidant assays were performed to better understand the effect of astaxanthin on cell growth and function.
Exposure to astaxanthin alone resulted in a mild to pronounced attenuation of cell proliferation in vitro, depending on the cell line, and did not interfere with the cell-death response to doxorubicin, irradiation, or peroxide-mediated insult. In some instances, astaxanthin acted in an additive fashion to augment cell death. Astaxanthin exposure increased the antioxidant potential of cells, whereas peroxide-mediated cell stress increased the antioxidant potential to the same degree as astaxanthin exposure or greater. No dramatic changes in phosphorylation of protein kinase B or upregulation of connexin 43 were detected.
Findings suggested that astaxanthin administration may be beneficial in treatment of dogs for osteosarcoma. Its actions as an antioxidant did not improve osteosarcoma cell survival during chemotherapeutic or irradiation insults, warranting further research into this natural compound as an adjuvant, antiproliferative treatment for osteosarcoma in dogs.
确定抗氧化剂虾青素对有或无同步化疗或放疗损伤的犬骨肉瘤细胞生长的影响。
来自3种已建立的犬骨肉瘤细胞系(D17、OS 2.4和HMPOS)的细胞。
通过各种治疗组合和3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐检测法评估生长曲线动力学和细胞细胞毒性作用。进行蛋白质印迹法以检测据报道虾青素会影响的先前确定的信号通路。此外,进行细胞周期动力学评估、软琼脂集落形成试验和抗氧化剂试验,以更好地了解虾青素对细胞生长和功能的影响。
单独暴露于虾青素会导致体外细胞增殖出现轻度至明显的减弱,具体取决于细胞系,并且不会干扰对阿霉素、放疗或过氧化物介导的损伤的细胞死亡反应。在某些情况下,虾青素以相加方式作用以增强细胞死亡。暴露于虾青素会增加细胞的抗氧化潜力,而过氧化物介导的细胞应激会使抗氧化潜力增加到与虾青素暴露相同或更高的程度。未检测到蛋白激酶B磷酸化或连接蛋白43上调有显著变化。
研究结果表明,给予虾青素可能对犬骨肉瘤的治疗有益。其作为抗氧化剂的作用并未改善化疗或放疗损伤期间骨肉瘤细胞的存活,这值得对这种天然化合物作为犬骨肉瘤的辅助抗增殖治疗进行进一步研究。