Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non-small-cell lung cancer cells

Toshiaki Ohara, Munenori Takaoka, Shinichi Toyooka, Yasuko Tomono, Toshio Nishikawa, Yasuhiro Shirakawa, Tomoki Yamatsuji, Noriaki Tanaka, Toshiyoshi Fujiwara, Yoshio Naomoto

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Abstract

Temsirolimus (CCI-779), a recently synthesized analogue of rapamycin, specifically inhibits mTOR and has been approved for clinical use in renal cell carcinoma. Recent reports have indicated the growth inhibitory effect of temsirolimus in some cancers including non-small-cell lung carcinoma (NSCLC). In this study, we aimed to explore the potential therapeutic use of temsirolimus as a treatment for NSCLC. Using cultured NSCLC cells (A549, H1299, and H358), we determined the effect of temsirolimus on cell proliferation and its antitumor effects on subcutaneous tumors, as well as its contribution to the survival of mice having pleural dissemination of cancer cells, mimicking advanced NSCLC. Temsirolimus suppressed proliferation of NSCLC cells in a dose-dependent manner, with an IC50 of 0/G1 phase, but according to flow cytometry, the cell population did not increase in the sub-G0 phase. When NSCLC subcutaneous tumor-bearing mice were treated with temsirolimus, tumor volume was significantly reduced (tumor volume on day 35: vehicle vs temsirolimus=1239 vs 698cm3; P

Original languageEnglish
Pages (from-to)1344-1349
Number of pages6
JournalCancer Science
Volume102
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Non-Small Cell Lung Carcinoma
Tumor Burden
Neoplasms
Cell Cycle Resting Phase
temsirolimus
G1 Phase
Therapeutic Uses
Sirolimus
Renal Cell Carcinoma
Inhibitory Concentration 50
Flow Cytometry
Cell Proliferation
Growth
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non-small-cell lung cancer cells. / Ohara, Toshiaki; Takaoka, Munenori; Toyooka, Shinichi; Tomono, Yasuko; Nishikawa, Toshio; Shirakawa, Yasuhiro; Yamatsuji, Tomoki; Tanaka, Noriaki; Fujiwara, Toshiyoshi; Naomoto, Yoshio.

In: Cancer Science, Vol. 102, No. 7, 07.2011, p. 1344-1349.

Research output: Contribution to journalArticle

Ohara, Toshiaki ; Takaoka, Munenori ; Toyooka, Shinichi ; Tomono, Yasuko ; Nishikawa, Toshio ; Shirakawa, Yasuhiro ; Yamatsuji, Tomoki ; Tanaka, Noriaki ; Fujiwara, Toshiyoshi ; Naomoto, Yoshio. / Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non-small-cell lung cancer cells. In: Cancer Science. 2011 ; Vol. 102, No. 7. pp. 1344-1349.
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