Cervical cancer patient-derived orthotopic xenograft (PDOX) is sensitive to cisplatinum and resistant to nab-paclitaxel

Takashi Murakami, Takuya Murata, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi, Ho Kyoung Hwang, Yukihiko Hiroshima, Chihiro Hozumi, Shin Komatsu, Takashi Kikuchi, Thinzar M. Lwin, Jonathan C. DeLong, Kentaro Miyake, Yong Zhang, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective. Materials and Methods: Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX. Results: H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors. Conclusion: The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.

Original languageEnglish
Pages (from-to)61-65
Number of pages5
JournalAnticancer research
Volume37
Issue number1
DOIs
Publication statusPublished - 2017 Jan

Keywords

  • Cervical cancer
  • Cispatinum
  • Drug response
  • Nab-paclitaxel
  • Nude mice
  • PDOX
  • Patient-derived othotopic xenograft

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Cervical cancer patient-derived orthotopic xenograft (PDOX) is sensitive to cisplatinum and resistant to nab-paclitaxel'. Together they form a unique fingerprint.

Cite this