Antitumor effect and antiangiogenic potential of the mTOR inhibitor temsirolimus against malignant pleural mesothelioma

Moriya,Makio; Yamada,Tadaaki; Tamura,Masaya; Ishikawa,Daisuke; Hoda,Mir Alireza; Matsumoto,Isao; Klepetko,Walter; Oda,Makoto; Yano,Seiji; Watanabe,Go

doi:10.3892/or.2013.2948

2014-March Volume 31 Issue 3

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2014-March Volume 31 Issue 3

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Article

Antitumor effect and antiangiogenic potential of the mTOR inhibitor temsirolimus against malignant pleural mesothelioma

Authors:
- Makio Moriya
- Tadaaki Yamada
- Masaya Tamura
- Daisuke Ishikawa
- Mir Alireza Hoda
- Isao Matsumoto
- Walter Klepetko
- Makoto Oda
- Seiji Yano
- Go Watanabe
View Affiliations / Copyright

Affiliations: Department of General and Cardiothoracic Surgery, Kanazawa University, Kanazawa, Japan, Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Pages: 1109-1115
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Published online on: December 30, 2013

https://doi.org/10.3892/or.2013.2948
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Abstract

The mTOR inhibitor temsirolimus has antitumor and antiangiogenic activity against several carcinomas, yet few reports document the efficacy of temsirolimus against malignant pleural mesothelioma (MPM). Therefore, we evaluated the efficacy of temsirolimus and the antiangiogenic effect of temsirolimus in the treatment of MPM. We examined the efficacy of temsirolimus alone and the efficacy of the combination of temsirolimus and cisplatin or pemetrexed against four MPM cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The effect of temsirolimus on the production of proangiogenic cytokines by MPM cell lines was examined by enzyme-linked immunosorbent assay (ELISA). Expression of mTOR and proangiogenic cytokines in clinical specimens from MPM patients was determined by immunohistochemistry. Temsirolimus inhibited cell viability and suppressed cell proliferation of all MPM cell lines. Combined treatment with temsirolimus and cisplatin inhibited the viability of all MPM cell lines more effectively than temsirolimus alone. Temsirolimus strongly inhibited the phosphorylation of p70s6k, a downstream molecule of mTOR, in all MPM cell lines and led to an increase in the levels of cleaved caspase-3 in the H226 and Y-meso14 cells. Temsirolimus also inhibited the production of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-AA (PDGF-AA). Phosphorylated mTOR and high expression of VEGF and PDGF were detected in 2 and 3, respectively, out of the 5 MPM specimens. These results suggest that temsirolimus has activity against MPM cells by inhibition of cell proliferation and angiogenesis, and may be beneficial for a subset of MPM patients with high mTOR expression.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Antitumor effect and antiangiogenic potential of the mTOR inhibitor temsirolimus against malignant pleural mesothelioma

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