Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction.
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.
Okui
Tatsuo
T
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
Shimo
Tsuyoshi
T
Fukazawa
Takuya
T
Kurio
Naito
N
Hassan
Nur Mohammad Monsur
NM
Honami
Tatsuki
T
Takaoka
Munenori
M
Naomoto
Yoshio
Y
Sasaki
Akira
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus