AB062. COX-2 inhibitors, a potential synergistic effect with antineoplastic drugs in lung cancer

Background: Lung cancer represents the leading cause of cancer-related deaths worldwide and novel therapeutic approaches targeting crucial pathways are urgently needed to improve its treatment. Inflammation plays a critical role in multistage tumor development and increased evidence has supported the involvement of cyclooxygenase-2 expression in carcinogenesis. We investigated the potential use of COX-2 inhibitors in cancer proliferation and apoptosis.

Methods: Celecoxib, rofecoxib, etoricoxib, meloxicam, ibuprofen and indomethacin are the COX-2 inhibitors included in this study. Docetaxel and Cisplatin are the chemotherapeutic agents that we combined with COX-2 inhibitors. Lung cancer cell lines (NCI-H1048-small cell lung cancer, A549-non-small cell lung cancer) were purchased from ATCC LGC standards. At indicated time-point, following 24 and 48 h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism.

Results: In small cell lung cancer cells, following 24 h incubation, combinations of docetaxel and meloxicam, docetaxel and ibuprofen, docetaxel and indomethacin, showed increased apoptosis when compared to docetaxel alone (P<0.0001). In non-small cell lung cancer cells, the 24 h incubation was not enough to induce satisfactory apoptosis, but following 48 h incubation, docetaxel plus indomethacin showed more cytotoxicity when compared to docetaxel alone (P<0.0001). In addition, the combination of cisplatin plus indomethacin was the only combination to be found with higher cytotoxicity when compared to cisplatin alone after 48 h treatment (P<0.0001).

Conclusions: Depending on the drug, the synergistic effect of COX-2 inhibitors plus chemotherapeutic agents has been demonstrated in lung cancer. Our suggestion is that COX-2 inhibitors could be used as additive and maintenance treatment in combination to antineoplastic agents in lung cancer patients.

Keywords: Lung cancer; COX-2 inhibitors; synergistic effect