Evaluating the synergistic effects of cisplatin and tamoxifen in canine osteosarcoma cells
Abstract
Introduction: Canine osteosarcoma is an aggressive primary bone tumor with a high metastatic rate and poor long-term prognosis. Therapeutic resistance remains a major cause of treatment failure. In human osteosarcoma, sex hormones influence tumor survival and proliferation, and emerging evidence suggests a similar role in canine osteosarcoma. Tamoxifen, a selective estrogen receptor modulator, inhibits estrogen receptor signaling and also exhibits estrogen-independent effects, including suppression of multidrug resistance pathways. Cisplatin is commonly used in canine osteosarcoma treatment; however, resistance limits its effectiveness. Therefore, we hypothesized that tamoxifen could enhance cisplatin efficacy through estrogen-independent mechanisms. Methods: Canine osteosarcoma cells were treated with a matrix of tamoxifen and cisplatin concentrations. Cell viability was assessed at 12, 24, and 48 hours using metabolic assays. Cleaved caspase activation and apoptosis-inducing factor expression were evaluated as markers of cell death, while Cyclin D1 and Ki-67 were assessed as markers of cell proliferation. Drug interaction was analyzed using the Zero Interaction Potency model. Results: Synergy analysis at 24 hours demonstrated strong synergistic activity between tamoxifen and cisplatin, with a ZIP score of 16.82. Combination treatment reduced metabolic activity and activated apoptotic markers at lower drug concentrations compared with either treatment alone. Although…
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