PURPOSE: Our previous study showed that peroxisome proliferator-activated receptor (PPAR) gamma induced the growth arrest and apoptosis of lung cancer cells. However, whether PPAR gamma ligands can inhibit the growth-promoting function of NNK is unknown.
METHODS: To address the above question, we used NCI-H23 lung cancer cells as the model to study how troglitazone (TGZ), a ligand of PPAR gamma, influenced the function of NNK.
RESULTS: Results showed that NNK stimulated cell proliferation, induced the DNA binding activity of nuclear factor-kB (NF-kB), down-regulated Bad expression, and up-regulated PPAR gamma protein expressions. Inhibition of NF-kB nuclear translocation led to the suppression of NNK-mediated Bad expression, indicating that NNK may regulate Bad expression through the activation of NF-kB. TGZ significantly inhibited cell proliferation induced by NNK. Though TGZ did not affect NF-kB activity, it up-regulated Bad expression.
CONCLUSION: Taken together, TGZ can efficiently inhibit the proliferation of lung cancer cells induced by NNK via Bad- and PPAR gamma-related pathways, which may not be directly relevant to the activity of NF-kB.
CLINICAL IMPLICATIONS: The finding may help to develop a new therapy for lung cancer.
DISCLOSURE: George Chen, None.