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.
Highlights
Osteosarcoma (OSA) represents the most common primary bone tumor in pet dogs
Ciprofloxacin or enrofloxacin decreases total viable cell number of canine OSA cells We investigated the effect of CPFX or ENFX on three different canine OSA cell lines
Ciprofloxacin or enrofloxacin induces S-G2/M arrest Based on the similarity in sensitivity between canine OSA cell lines, we chose to focus mechanistic studies on Abrams cells
Summary
Osteosarcoma (OSA) represents the most common primary bone tumor in pet dogs. As an alternative to amputation, limb-salvage procedures can provide adequate local control and yield median survival times similar to those reported in dogs undergoing amputation. While postoperative limb-spare infections are quite common in the dog, multiple studies have found such infections to be associated with improved survival when compared with treated dogs without infection [3,4,5]. One such study reported that 24 out of 32 dogs experiencing post-operative allograft infections were treated with fluoroquinolone antibiotics [3], a class of drugs known to have independent activity against several tissue and cancer cell lines in vitro and in vivo [6,7,8]. Some FQs have the ability to reverse multidrug resistance-associated protein mediated drug resistance [10], promote microRNA processing [11], induce immunomodulatory effects [12], and are cytotoxic to vascular endothelial cells [13]; indicating that they may possess both direct and indirect antitumor activity when used in combination with traditional chemotherapy
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