Back to Search
Start Over
Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.
- Source :
-
Anti-cancer drugs [Anticancer Drugs] 2014 Mar; Vol. 25 (3), pp. 332-9. - Publication Year :
- 2014
-
Abstract
- Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (P<0.001) and decreased tumor growth (P<0.001). Pulmonary macrometastasis and Ki67 labeling were reduced with low-dose aurothiomalate (P=0.033 and 0.005, respectively), and tumor emboli and pulmonary micrometastases were decreased with high-dose aurothiomalate (P=0.010 and 0.011, respectively). There was no difference in survival, tumor development, ulceration, mitotic indices, tumor necrosis, nonpulmonary metastases, and caspase-3 labeling. Aurothiomalate treatment inhibited osteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Apoptosis drug effects
Bone Neoplasms pathology
Caspase 3 metabolism
Cell Proliferation drug effects
Cell Survival drug effects
Dogs
Gold Sodium Thiomalate pharmacology
Humans
Ki-67 Antigen metabolism
Lung Neoplasms drug therapy
Lung Neoplasms secondary
Mice
Osteosarcoma pathology
Xenograft Model Antitumor Assays
Antineoplastic Agents therapeutic use
Bone Neoplasms drug therapy
Gold Sodium Thiomalate therapeutic use
Osteosarcoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5741
- Volume :
- 25
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Anti-cancer drugs
- Publication Type :
- Academic Journal
- Accession number :
- 24304691
- Full Text :
- https://doi.org/10.1097/CAD.0000000000000061