Antitumor activity from the combined application of poly(I:C) and chemotherapeutics in human metastatic pharyngeal cell lines.

ABSTRACT

BACKGROUND: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(IC)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. METHODS: Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. RESULTS: We found that the combined application of poly(IC) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. CONCLUSION: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.