chemotherapeutic drugs induce ppar-γ expression and show sequence-specific synergy with ppar-γ ligands in inhibition of non–small cell lung cancer

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ID: 134081
2008
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Abstract
Preclinical studies have shown that peroxisome proliferator–activated receptor γ (PPAR-γ) ligands can exert antitumor effects against non–small cell lung cancer (NSCLC) and a variety of other cancers. In this study, we investigate the potential use of a PPAR-γ ligand, troglitazone (Tro), in combination with either of two chemotherapeutic agents, cisplatin (Cis) or paclitaxel (Pac), for the treatment of NSCLC. In vitro, treatment of NSCLC cell lines with Tro potentiated Cis- or Pac-induced growth inhibition. The potentiation of growth inhibition was observed only when Cis or Pac treatment was followed by Tro and not vice versa, demonstrating a sequence-specific effect. Median effect analysis revealed a synergistic interaction between Tro and Cis in the inhibition of NSCLC cell growth and confirmed the sequence-specific effect. We also found that Cis or Pac up-regulated the expression of PPAR-γ protein, accounting for the observed sequence-specific synergy. Similarly, experiments performed using a NSCLC xenograft model demonstrated enhanced effectiveness of combined treatment with Cis and PPAR-γ ligands, Tro or pioglitazone. Tumors from Cis-treated mice also demonstrated enhanced PPAR-γ expression. Together, our data demonstrate a novel sequence-specific synergy between PPAR-γ ligands and chemotherapeutic agents for lung cancer treatment.
Reference Key
reddy2008neoplasia:chemotherapeutic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Raju C. Reddy;Anjaiah Srirangam;Kaunteya Reddy;Jun Chen;Srinivasareddy Gangireddy;Gregory P. Kalemkerian;Theodore J. Standiford;Venkateshwar G. Keshamouni
Journal ACS chemical neuroscience
Year 2008
DOI
10.1593/neo.08134
URL
http://www.sciencedirect.com/science/article/pii/S1476558608801480
Keywords
neoplasms Oncology including cancer and carcinogens tumors

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