Molecular Cancer apeutics apeutic Discovery itumor Effect of Temsirolimus against Oral Squamous Cell Ther cinoma Associated with Bone Destruction

ownload mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous rcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR tor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, vestigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral ous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous rcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. icantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. se transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor tor for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral calcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell hyper carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma. Mol Cancer Ther; 9(11); 2960–9. ©2010 AACR.