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Toll-like receptor 3, uz ostale receptore "Toll-like" (TLR, od engl. Toll-like receptors), ima ključnu ulogu u urođenoj imunosti. Nedavna istraživanja pokazala su da se TLR3, kao i ostali srodni receptori, nalazi izražen i u stanicama određenih vrsta tumora, te da njegova aktivacija potiče apotozu stanica tumora i inhibira njihovu proliferaciju. Također je otkriveno da aktivacija TLR3 u kombinaciji s protutumorskim terapeuticima povećava citotoksični učinak agonista TLR3 na stanice tumora. To dovodi do zaključka da se agonisti TLR3 mogu koristiti kao protutumorski agensi zbog svojeg citostatskog i citotoksičnog djelovanja na stanice tumora. U ovom istraživanju ispitali smo djelovanje liganda TLR3, poliriboinozilne:poliribocitidilne kiseline (poly(I:C)), u kombinaciji s kemoterapeuticima 5-fluorouracilom i metotreksatom, na stanice primarnog i metastatskog tumora ždrijela. Svrha ovog rada jest ispitati mogućnost kombinirane primjene poly(I:C) i kemoterapeutika kao protutumorske terapije. Prema dobivenim rezultatima ustanovili smo da kombinirana primjena poly(I:C) i kemoterapeutika ima značajno veći inhibitorni učinak na stanice nego zasebni tretman s poly(I:C), tj. da poly(I:C) i kemoterapeutici 5-fluorouracil i metotreksat djeluju sinergistički. Također smo utvrdili da je inhibitorni učinak kombiniranog tretmana s poly(I:C) i kemoterapeuticima posljedica poly(I:C)-aktivirane apoptoze ovisne o TLR3-signalnom putu. Toll-like receptor 3, as well as other TLRs, plays a key role in innate immunity. Recent studies have shown that TLR3 is expressed on certain types of tumor cells and that its activation stimulates apotosis of tumor cells and inhibits their proliferation. Also it has been found that activation of TLR3 in combination with antitumor therapeutics increases the cytotoxic effect of TLR3 agonist on tumor cells. This leads to the conclusion that the TLR3 agonists can be used as antitumor agents because of their citostatic and cytotoxic effects on tumor cells. In this study, we investigated the effect of TLR3 ligand, polyinosinic:polycytidylic acid (poly(I:C)), in combination with chemotherapeutics 5-fluorouracil and methotrexate on primary and metastatic pharyngeal carcinoma cell lines. The purpose of this study was to examine the possibility of combined application of poly(I:C) and chemotherapeutics as an antitumor therapy. We have found that combined application of poly(I:C) and chemotherapeutics has a significantly greater inhibitory effect on cell growth than the separate treatment with poly(I:C), i.e. poly(I:C) and chemotherapeutics act synergistically. We also found that the inhibitory effect of combined treatment with poly(I:C) and chemotherapeutics is a result of TLR3-dependent apoptosis. |
