A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model.
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.
['Igarashi|Kentaro|K|', 'Kawaguchi|Kei|K|', 'Yamamoto|Norio|N|', 'Hayashi|Katsuhiro|K|', 'Kimura|Hiroaki|H|', 'Miwa|Shinji|S|', 'Higuchi|Takashi|T|', 'Taniguchi|Yuta|Y|', 'Yonezawa|Hirotaka|H|', 'Araki|Yoshihiro|Y|', 'Morinaga|Sei|S|', 'Misra|Sweta|S|', 'Nelson|Scott D|SD|', 'Dry|Sarah M|SM|', 'Li|Yunfeng|Y|', 'Odani|Akira|A|', 'Singh|Shree Ram|SR|', 'Tsuchiya|Hiroyuki|H|', 'Hoffman|Robert M|RM|']
D000293:Adolescent D000818:Animals D000838:Anions D000970:Antineoplastic Agents D001859:Bone Neoplasms D002470:Cell Survival D002945:Cisplatin D019008:Drug Resistance, Neoplasm D006801:Humans D051379:Mice D008819:Mice, Nude D009944:Organoplatinum Compounds D012516:Osteosarcoma D010710:Phosphates D047368:Tumor Burden D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
cisplatinum-resistant Osteosarcoma 3Pt efficacy PDOX platinum complex