The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo

Makiko Nakatani, Hidemichi Watari, Takashi Mitamura, Lei Wang, Yutaka Hatanaka, Kanako C. Hatanaka, Kohei Honda, Toshiyuki Nomura, Hiroshi Nishihara, Shinya Tanaka, Noriaki Sakuragi

Research output: Contribution to journalArticle

Abstract

Background: Several reports have shown that the overexpression of the MET proto-oncogene, receptor tyrosine kinase (MET), was more frequently observed in clear cell carcinoma (CCC) than in non-CCC. We evaluated the antitumor activity of cabozantinib, that targets MET. Materials and Methods: A gene expression analysis of tumors from human ovarian cancers was carried out by transcriptome sequencing. An in vitro 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay (MTT assay) and in vivo experiments were performed to determine the activity of cabozantinib. Results: The MET levels were higher in tumors with CCC than high-grade serous carcinoma (2.2-fold). Cabozantinib inhibited cell viability and phosphorylation of AKT and MAPK under the treatment of hepatocyte growth factor in RMG-I CCC cells. The tumors removed from mice given cabozantinib of 10 mg/kg weighed 70% less than control on day 15, and the immunohistochemical reactivity of phosphorylated MET was reduced compared with control mice. Conclusion: Cabozantinib contributes to tumor reduction, and phosphorylated MET represents an attractive target of CCC.

Original languageEnglish
Pages (from-to)6125-6132
Number of pages8
JournalAnticancer research
Volume37
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1
Externally publishedYes

Fingerprint

Carcinoma
Neoplasms
Proto-Oncogene Proteins c-met
Hepatocyte Growth Factor
Bromides
Transcriptome
Ovarian Neoplasms
In Vitro Techniques
cabozantinib
Cell Survival
Phosphorylation
Gene Expression

Keywords

  • Cabozantinib
  • Clear cell carcinoma
  • MET
  • Ovarian cancer
  • RMG-I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nakatani, M., Watari, H., Mitamura, T., Wang, L., Hatanaka, Y., Hatanaka, K. C., ... Sakuragi, N. (2017). The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo. Anticancer research, 37(11), 6125-6132. https://doi.org/10.21873/anticanres.12061

The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo. / Nakatani, Makiko; Watari, Hidemichi; Mitamura, Takashi; Wang, Lei; Hatanaka, Yutaka; Hatanaka, Kanako C.; Honda, Kohei; Nomura, Toshiyuki; Nishihara, Hiroshi; Tanaka, Shinya; Sakuragi, Noriaki.

In: Anticancer research, Vol. 37, No. 11, 01.11.2017, p. 6125-6132.

Research output: Contribution to journalArticle

Nakatani, M, Watari, H, Mitamura, T, Wang, L, Hatanaka, Y, Hatanaka, KC, Honda, K, Nomura, T, Nishihara, H, Tanaka, S & Sakuragi, N 2017, 'The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo', Anticancer research, vol. 37, no. 11, pp. 6125-6132. https://doi.org/10.21873/anticanres.12061
Nakatani M, Watari H, Mitamura T, Wang L, Hatanaka Y, Hatanaka KC et al. The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo. Anticancer research. 2017 Nov 1;37(11):6125-6132. https://doi.org/10.21873/anticanres.12061
Nakatani, Makiko ; Watari, Hidemichi ; Mitamura, Takashi ; Wang, Lei ; Hatanaka, Yutaka ; Hatanaka, Kanako C. ; Honda, Kohei ; Nomura, Toshiyuki ; Nishihara, Hiroshi ; Tanaka, Shinya ; Sakuragi, Noriaki. / The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo. In: Anticancer research. 2017 ; Vol. 37, No. 11. pp. 6125-6132.
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