| RRC ID |
18700
|
| 著者 |
Okui T, Shimo T, Fukazawa T, Kurio N, Hassan NM, Honami T, Takaoka M, Naomoto Y, Sasaki A.
|
| タイトル |
Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction.
|
| ジャーナル |
Mol Cancer Ther
|
| 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.
|
| 巻・号 |
9(11)
|
| ページ |
2960-9
|
| 公開日 |
2010-11-1
|
| DOI |
10.1158/1535-7163.MCT-10-0489
|
| PII |
1535-7163.MCT-10-0489
|
| PMID |
20858724
|
| MeSH |
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Bone Neoplasms / complications
Bone Neoplasms / drug therapy
Bone Neoplasms / secondary
Bone Resorption / etiology
Bone Resorption / pathology
Bone Resorption / prevention & control*
Carcinoma, Squamous Cell / complications*
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / pathology*
Cell Movement / drug effects
Cells, Cultured
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms / complications*
Mouth Neoplasms / drug therapy
Mouth Neoplasms / pathology*
Osteoclasts / drug effects
Osteoclasts / pathology
Osteoclasts / physiology
Sirolimus / analogs & derivatives*
Sirolimus / pharmacology
Sirolimus / therapeutic use
Xenograft Model Antitumor Assays
|
| IF |
5.615
|
| 引用数 |
20
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224)
RAW 264(RCB0535) |
