Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction

Tatsuo Okui, Tsuyoshi Shimo, Takuya Fukazawa, Naito Kurio, Nur Mohammad Monsur Hassan, Tatsuki Honami, Munenori Takaoka, Yoshio Naomoto, Akira Sasaki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous cell carcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR inhibitor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, we investigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral squamous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. Significantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. Reverse transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor activator for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 cells. Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral hypercalcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma.

Original languageEnglish
Pages (from-to)2960-2969
Number of pages10
JournalMolecular cancer therapeutics
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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