Rapamycin Inhibits the Growth and Metastatic Progression of Non-Small Cell Lung Cancer

Daniel J. Boffa, Fulung Luan, Dolca Thomas, Hua Yang, Vijay K. Sharma, Milagros Lagman, Manikkam Suthanthiran

Research output: Contribution to journalArticle

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Abstract

Purpose: Lung cancer has a dismal prognosis and comprises 5.5% of post-transplant malignancies. We explored whether rapamycin inhibits the growth and metastatic progression of non-small cell lung cancer (NSCLC). Experimental Design: Murine KLN-205 NSCLC was used as the model tumor in syngeneic DBA/2 mice to explore the effect of rapamycin on tumor growth and metastastic progression. We also examined the effect of rapamycin on cell cycle progression, apoptosis, and proliferation using murine KLN-205 NSCLC cells and human A-549 NSCLC cells as targets. The in vivo and in vitro effects of cyclosporine and those of rapamycin plus cyclosporine were also investigated. Results: Rapamycin but not cyclosporine inhibited tumor growth; s.c. tumor volume was 1290 ± 173 mm3 in untreated DBA/2 mice, 246 ± 80 mm 3 in mice treated with rapamycin, and 1203 ± 227 mm 3 in mice treated with cyclosporine (P < 0.001). Rapamycin but not cyclosporine prevented the formation of distant metastases; eight of eight untreated mice and four of six mice treated with cyclosporine developed pulmonary metastases whereas only one of six mice treated with rapamycin developed pulmonary metastases (P = 0.003). In vitro, rapamycin induced cell cycle arrest at the G1 checkpoint and blocked proliferation of both KLN-205 and A-549 cells but did not induce apoptosis. Cyclosporine did not prevent cell cycle progression and had a minimal antiproliferative effect on KLN-205 and A-549 cells. Conclusions: The immunosuppressive macrolide rapamycin but not cyclosporine prevents the growth and metastatic progression of NSCLC. A rapamycin-based immunosuppressive regimen may be of value in recipients of allografts.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number1 I
DOIs
Publication statusPublished - 1 Jan 2004
Externally publishedYes

Fingerprint

Sirolimus
Non-Small Cell Lung Carcinoma
Cyclosporine
Growth
Inbred DBA Mouse
Immunosuppressive Agents
Neoplasm Metastasis
Neoplasms
Cell Cycle
Apoptosis
G1 Phase Cell Cycle Checkpoints
Lung
Macrolides
Tumor Burden
Allografts
Lung Neoplasms
Research Design
Transplants

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rapamycin Inhibits the Growth and Metastatic Progression of Non-Small Cell Lung Cancer. / Boffa, Daniel J.; Luan, Fulung; Thomas, Dolca; Yang, Hua; Sharma, Vijay K.; Lagman, Milagros; Suthanthiran, Manikkam.

In: Clinical Cancer Research, Vol. 10, No. 1 I, 01.01.2004, p. 293-300.

Research output: Contribution to journalArticle

Boffa, Daniel J. ; Luan, Fulung ; Thomas, Dolca ; Yang, Hua ; Sharma, Vijay K. ; Lagman, Milagros ; Suthanthiran, Manikkam. / Rapamycin Inhibits the Growth and Metastatic Progression of Non-Small Cell Lung Cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 1 I. pp. 293-300.
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