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Updated: Mar 8, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Therapeutic implication of mTORC2 in oral squamous cell carcinoma
Tomofumi Naruse1, Souichi Yanamoto1, Kohei Okuyama1
1Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
Abstract:
The aim of the present study was to clarify the association of mTORC2 expression with the cancer progression and the anti-tumor effects of Torin-1 alone and combined treatment with Cetuximab in OSCC cells. The expressions of Rictor and SGK1 were immunohistochemically evaluated and the relationships between the expressions of molecular markers and clinicopathological factors were determined. Moreover, OSCC cells were treated with Torin-1, Cetuximab or combined agents, and anti-tumor effects of OSCC cells were examined in vitro and in vivo. Rictor and SGK1 expressions were significantly associated with tumor stage and pattern of invasion in OSCC sections (P<0.05 and P<0.01, respectively). Treatment of OSCC cell lines with Torin-1 resulted in dose and time-dependent inhibition of proliferation with decrease of phosphorylation on downstream molecules. Combined treatment with Torin-1 and Cetuximab resulted in enhanced anti-tumor effects in vitro compared with either agent alone. Furthermore, treatment of mice bearing OSCC xenografts with Torin-1 and Cetuximab also demonstrated a remarked growth inhibition of tumor volumes. The results suggested that new regimens of systemic therapy combined with Cetuximab and Torin-1 may be useful for very advanced OSCC patients.
Insights
This study found that targeting mTORC2 with Torin-1 and Cetuximab inhibits oral squamous cell carcinoma (OSCC) progression. Combination therapy demonstrated significant anti-tumor effects in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The mammalian target of rapamycin complex 2 (mTORC2) pathway is implicated in various cancers.
- Understanding mTORC2's role in oral squamous cell carcinoma (OSCC) progression is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the association between mTORC2 expression and OSCC progression.
- To evaluate the anti-tumor efficacy of Torin-1, an mTORC2 inhibitor, alone and in combination with Cetuximab in OSCC cells.
Main Methods:
- Immunohistochemical evaluation of Rictor and SGK1 (mTORC2 components) in OSCC tissues.
- In vitro and in vivo experiments assessing the effects of Torin-1 and Cetuximab on OSCC cell lines and xenografts.
- Analysis of molecular markers and clinicopathological factors.
Main Results:
- Rictor and SGK1 expression levels correlated significantly with tumor stage and invasion patterns in OSCC.
- Torin-1 treatment inhibited OSCC cell proliferation in a dose- and time-dependent manner.
- Combined Torin-1 and Cetuximab treatment exhibited enhanced anti-tumor effects compared to monotherapy, both in vitro and in vivo, significantly inhibiting tumor growth.
Conclusions:
- mTORC2 signaling is linked to OSCC progression.
- Combination therapy with Torin-1 and Cetuximab shows promising anti-tumor activity against OSCC.
- This combination may represent a potential therapeutic strategy for advanced OSCC.
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