Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma

Author(s): Tatsuo Okui, Tsuyoshi Shimo, Takuya Fukazawa, Nur Mohammad Monsur Hassan, Tatsuki Honami, Soichiro Ibaragi, Munenori Takaoka, Yoshio Naomoto, Akira Sasaki.

Abstract:

Background and Aim: Heat shock protein 90 (HSP90) and mammalian target of rapamycin (mTOR) are involved in the molecular pathogenesis of advanced oral squamous cell carcinoma. HSP90 inhibitors are capable of effectively interfering with multiple signaling pathways, including the mTOR signaling pathway. However, the combined effects of HSP90 and mTOR inhibitors on oral squamous cell carcinoma are still unknown. In this study, we investigated the dual treatment of the novel HSP90 inhibitor NVP-AUY922 and temsirolimus against oral squamous cell carcinoma.

Materials and Methods: The effect of the combination of NVP-AUY922 and temsirolimus on oral squamous cell carcinoma in vitro and in vivo was determined by MTS assay and mouse xenograft models. The effect of the combination on angiogenesis was determined by tube formation assay and angioreactor.

Results: The combination treatment of NVP-AUY922 and temsirolimus significantly inhibited the proliferation of SAS oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. We have clearly shown that the combination treatment of NVP-AUY922 and temsirolimus inhibited vascular formation both in vitro and in vivo. Moreover, the combination treatment of NVP-AUY922 and temsirolimus prolonged the survival rate in mice xenografted with oral squamous cell carcinoma.

Conclusions: Here, we showed the activity of a combination of mTOR and HSP90 inhibitors for the treatment of advanced oral squamous carcinoma.

Keywords: Angiogenesis, combination treatment, HSP90 inhibitor, NVP-AUY922, oral squamous cell carcinoma, temsirolimus

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2013
Page: [289 - 299]
Pages: 11
DOI: 10.2174/1568009611313030007
Price: $58