Pharmacological activities of cyclooxygenase (COX) inhibitors against chlolangiocarcinoma

[Speaker] Wanna Chaijaroenkul:1,2
[Co-author] Kesara Na-Bangchang:1,2
1:Chulabhorn International College of Medicine, Thammasat University, Thailand, 2:Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thailand

Background: Cyclooxygenase (COX) enzyme is the key enzyme responsible for prostanoids production, which plays important role in inflammatory process and pathogenesis of several diseases including cancer. In this study, a series of both selective and non- selective COX-2 inhibitors, i.e, aspirin, ibuprofen, piroxicam, and naproxen were investigated their cytotoxic activities in vitro. Method: The cytotoxicity against cholangiocarcinoma (CCA) cell line (CL-6) was performed using MTT assay. Results: Median (range) IC50 values of aspirin, ibuprofen, piroxicam, naproxen, and 5-FU were 748.0 (522.2-1005.5), 1185.1 (700.6-1318), 1100.3 (759.7-1166.8), 1550.7 (1353.7-1797.3), and 366.8 (306.8-410.9) M, respectively. Results showed that non-specific COX inhibitors exhibited more potent activities against CCA than specific COX-2 inhibitors. This implies that not only COX-2, but also COX-1 may also involve in carcinogenesis of CCA. Aspirin significantly reversed resistance of CL-6 to 5-FU; the IC50 of 5-FU was decreased by approximately 2.6-fold following the exposure of CL-6 to aspirin (500 M). Moreover, the combination of aspirin and 5-FU showed synergism interaction, with sum FIC of 0.63 (0.61-0.82). Conclusions: COX inhibitors particularly aspirin could be used as therapeutic agent either as adjuvant or used in combination with other cytotoxic agents for CCA.
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