| Abstrakt: |
Summary: Purpose. Among the lung cancer types, non-small cell lung cancer (NSCLC) is prominent and less responsive to chemotherapy. The current chemotherapeutics for NSCLC are associated with several dose-limiting side effects like bone-marrow suppression, neurotoxicity, nephrotoxicity, and ototoxicity, etc. which are causing non-compliance in patients. Many tumors, including breasts, lung, ovarian, etc. overexpress PPAR-γ receptors and COX-2 enzymes, which play a crucial role in tumor progression, angiogenesis, and metastasis. Lack of PPAR-γ activation and overproduction of prostaglandins, result in uncontrolled activation of Ras/Raf/Mek ultimately, NF-κB mediated tumor proliferation. This study aimed to investigate the anti-cancer potential of PPAR-γ agonist Pioglitazone combined with COX-2 inhibitor Celelcoxib in NSCLC. Methods. Sixty adult Balb/C male mice were classified into sham control, disease control, and treatment groups. Mice were treated with Nicotine-derived nitrosamine ketone (NNK) (10 mg/kg), pioglitazone (10 & 20 mg/kg) and celecoxib (25 & 50 mg/kg). Weekly body weight, food intake, mean survival time & % increased life span were determined. Tumor weight and histopathological analysis were performed at the end of the study. Results. The significant tumor reducing potential of pioglitazone combined with celecoxib was observed (p < 0.05). The treatment groups (treated with pioglitazone and celecoxib) showed a remarkable decrease in lung tumor weight, improved life span and mean survival time (p < 0.05). Histopathological studies confirm that treatment groups (treated with pioglitazone and celecoxib) reframed the lung architecture compared to disease control. Conclusion. Preliminary results revealed that pioglitazone adjunacy with celecoxib may be an effective chemo-preventive agent against NNK induce NSCLC. [ABSTRACT FROM AUTHOR] |
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