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A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model
- IGARASHI, KENTARO;
- KAWAGUCHI, KEI;
- YAMAMOTO, NORIO;
- HAYASHI, KATSUHIRO;
- KIMURA, HIROAKI;
- MIWA, SHINJI;
- HIGUCHI, TAKASHI;
- TANIGUCHI, YUTA;
- YONEZAWA, HIROTAKA;
- ARAKI, YOSHIHIRO;
- MORINAGA, SEI;
- MISRA, SWETA;
- NELSON, SCOTT D;
- DRY, SARAH M;
- LI, YUNFENG;
- ODANI, AKIRA;
- SINGH, SHREE RAM;
- TSUCHIYA, HIROYUKI;
- HOFFMAN, ROBERT M
- et al.
Published Web Location
https://doi.org/10.21873/cgp.20182Abstract
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. 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. RESULTS:3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC50 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. CONCLUSION:3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma.
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