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Introduction: Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality. Multiple studies have indicated that specific cyclooxygenase 2 (COX-2) inhibitors may serve for the prevention and treatment of a variety of malignancies including NSCLC. Recent studies had shown that the long-term use of COX-2 inhibitors is not toxic free, and may be limited due to serious gastro-intestinal and cardio-vascular side effects. The anti-neoplastic efficacy of the phytochemical curcumin, a natural COX-2 inhibitor, has been demonstrated in several in vitro studies and animal models. The aims of this study are to evaluate the effect of curcumin in vitro on NSCLC as well as on growth and metastasis of orthotopic tumors from human NSCLC in athymic mice and to investigate a mechanism of curcumin action.

Materials and Methods: Human H1975 NSCLC cells were treated with curcumin (0-50 μM). Cell viability was evaluated by XTT assay. Apoptosis was assessed by flow cytometry. Expression of COX-2, EGFR, ErbB-2 and activity of p-Erk1/2 was measured by Western blotting analysis. For in vivo study, tumor cells in Matrigel were injected into the lung of CD-1 nude mice. The mice (n=10 per group) recieved either curcumin (0.6%) or control diet 14 days before tumor cells implantation. The mice were sacrificed at the time point when the control animals became moribund or followed up till death.

Results: Curcumin inhibited NSCLC cell growth in vitro and induced apoptosis in a dose dependent manner. Western blot analysis showed that COX-2 expression and Erk1/2 activity were down-regulated by curcumin treatment. Curcumin treatment produced 36% decrease in weight of lung cancers (p=0.048) and significant increase in survival rate (Hazard Ratio= 2.728, p=0.036).

Conclusions: Our data suggest that curcumin inhibits COX-2 expression and Erk1/2 activity in NSCLC cells. This inhibition is associated with decreased survival and enhanced induction of apoptosis. Curcumin has shown to significantly reduce the growth of orthotopic human non-small cell lung tumors and improve survival of athymic mice. This may pave the way for clinical trial to evaluate curcumin role in chemoprevention and treatment of this devastating disease.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA