The effect of thalidomide on non-small cell lung cancer (NSCLC) cell lines: Possible involvement in the PPARγ pathway

Kathleen L. DeCicco, Takemi Tanaka, Fausto Andreola, Luigi M De Luca

Research output: Contribution to journalArticle

Abstract

Lung cancer is the leading cause of cancer-related death in developed countries. Non-small cell lung cancer (NSCLC) represents 80% of the total lung cancer cases and is comprised of adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma and large cell carcinoma (LCC) subtypes. The ability of LCC to metastasize earlier than the other forms of lung cancer suggests anti-angiogenic drugs as effective agents to combat this cancer. Thalidomide is an anti-angiogenic drug that has shown promise in multiple hematological diseases, and myeloma and other cancers. However, the molecular mechanism by which thalidomide exerts its effects is poorly understood. Therefore, we evaluated the effectiveness of thalidomide on NSCLC cell growth, and found that LCC cells were growth inhibited by 40-60%. This effect seemed specific to LCC cancer cells, since other forms of NSCLC were only mildly affected by thalidomide. At the molecular level, thalidomide increased peroxisome proliferator-activated receptor gamma (PPARγ) protein dose-dependently, and peroxisome proliferator response element activity. Further, thalidomide treatment of LCC cells decreased nuclear factor kappa B activity in a dose-dependent fashion, increased apoptosis and decreased the expression of angiogenic proteins. In our mouse xenograft model of lung cancer, we found that intratumoral thalidomide caused a 64% decrease in tumor growth; moreover, tumors from the thalidomide-treated mice expressed higher PPARγ, than tumors from control mice. This study shows the antitumor activity of thalidomide against LCC tumors and suggests a model in which thalidomide exerts its antitumor effects on LCC cells through the induction of PPARγ and subsequent downstream signaling. To our knowledge, this is the first study to show a link between thalidomide and PPARγ.

Original languageEnglish (US)
Pages (from-to)1805-1812
Number of pages8
JournalCarcinogenesis
Volume25
Issue number10
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Thalidomide
PPAR gamma
Non-Small Cell Lung Carcinoma
Large Cell Carcinoma
Cell Line
Lung Neoplasms
Neoplasms
Angiogenesis Inhibitors
Growth
Angiogenic Proteins
Adenosquamous Carcinoma
Peroxisome Proliferators
Hematologic Diseases
NF-kappa B
Response Elements
Developed Countries
Heterografts
Squamous Cell Carcinoma
Adenocarcinoma
Apoptosis

ASJC Scopus subject areas

  • Cancer Research

Cite this

The effect of thalidomide on non-small cell lung cancer (NSCLC) cell lines : Possible involvement in the PPARγ pathway. / DeCicco, Kathleen L.; Tanaka, Takemi; Andreola, Fausto; De Luca, Luigi M.

In: Carcinogenesis, Vol. 25, No. 10, 10.2004, p. 1805-1812.

Research output: Contribution to journalArticle

DeCicco, Kathleen L. ; Tanaka, Takemi ; Andreola, Fausto ; De Luca, Luigi M. / The effect of thalidomide on non-small cell lung cancer (NSCLC) cell lines : Possible involvement in the PPARγ pathway. In: Carcinogenesis. 2004 ; Vol. 25, No. 10. pp. 1805-1812.
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