fluoroquinolone-mediated inhibition of cell growth, s-g2m cell cycle arrest, and apoptosis in canine osteosarcoma cell linesfluoroquinolone-mediated抑制细胞生长,s-g2m细胞周期阻滞和细胞凋亡在犬骨肉瘤细胞系.pdfVIP

Fluoroquinolone-Mediated Inhibition of Cell Growth, S-G2/M Cell Cycle Arrest, and Apoptosis in Canine Osteosarcoma Cell Lines 1,2 2 2 2 2 Kyoung won Seo , Roseline Holt , Yong-Sam Jung , Carlos O. Rodriguez Jr. , Xinbin Chen , Robert B. Rebhun2* 1 Department of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, California, United States of America, 2 Department of Internal Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea Abstract Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21WAF1 expression resulting in decreased proliferation and increased S-G2/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma. Citation: Seo Kw, Holt R, Jung Y-S, Rodriguez CO Jr, Chen X,