A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model

Kentaro Igarashi, Kei Kawaguchi, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Takashi Higuchi, Yuta Taniguchi, Hirotaka Yonezawa, Yoshihiro Araki, Sei Morinaga, Sweta Misra, Scott D. Nelson, Sarah M. Dry, L. I. Yunfeng, Akira Odani, Shree R.A.M. Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalCancer Genomics and Proteomics
Volume17
Issue number3
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • 3Pt
  • Cisplatinum-resistant
  • Efficacy
  • Osteosarcoma
  • PDOX
  • Platinum complex

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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