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A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model.
- Source :
-
Cancer genomics & proteomics [Cancer Genomics Proteomics] 2020 May-Jun; Vol. 17 (3), pp. 217-223. - Publication Year :
- 2020
-
Abstract
- Background/aim: We have previously developed a novel bone-targeting platinum compound, 3Pt, and showed that it has strong inhibitory activity against osteosarcoma cells and orthotopic cell-line xenograft mouse models. In the present report, we compared the efficacy of 3Pt to cisplatinum (CDDP) in a CDDP-resistant relapsed osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model.<br />Patients and Methods: The tumor of a patient with osteosarcoma of the distal femur was treated with CDDP-based chemotherapy followed by surgery. The surgical specimen was used to establish a PDOX model. An osteosarcoma cell line was also established from the original patient tumor. Osteosarcoma cell viability was assessed with the WST-8 assay and the IC50 values were calculated. The PDOX models were randomized into three groups: untreated control, CDDP-treated group, and 3Pt-treated group. Tumor size and body weight were measured twice a week.<br />Results: 3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC <subscript>50</subscript> value of 3Pt was significantly lower than that of CDDP. On day 14 of the treatment, 3Pt caused a significantly greater tumor growth inhibition compared to the untreated control and CDDP-treated mice.<br />Conclusion: 3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma.<br /> (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Adolescent
Animals
Anions chemistry
Antineoplastic Agents chemistry
Bone Neoplasms pathology
Cell Survival
Cisplatin pharmacology
Drug Resistance, Neoplasm
Humans
Mice
Mice, Nude
Organoplatinum Compounds chemistry
Osteosarcoma pathology
Phosphates chemistry
Tumor Burden drug effects
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Bone Neoplasms drug therapy
Organoplatinum Compounds pharmacology
Osteosarcoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1790-6245
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer genomics & proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 32345663
- Full Text :
- https://doi.org/10.21873/cgp.20182