Enhanced sensitivity of prostate cancer cells to tumor necrosis factor-ralated apoptosisinducing
ligand (TRAIL) mediated cytotoxicity by taxanes
Article published in Urologia Polska 2008/61/Supl. 1.
Ewelina Szliszka, Joanna Bronikowska, Anatol Majcher, Jerzy Miszkiewicz, Wojciech Król
- Katedra i Zakład Mikrobiologii i Immunologii w Zabrzu, ¦l±ski Uniwersytet Medyczny w Katowicach
Introduction. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis in a variety of transformed cells with no toxicity against normal tissues.
Objectives. Cancer cells that are resistant to TRAIL induced apoptosis can be sensitized by chemotherapeutic drugs.
Materials and methods. Three human prostate cancer cell lines: LNCaP, DU145, PC3 were incubated with TRAIL in the presence or absence of the chemotherapeutic agent: paclitaxel and docetaxel. Cytotoxicity was determined by MTT and LDH assay.
Results. Our study confirmed that all prostate cancer cell lines were resistant to TRAIL. We therefore examined the cytotoxic effect of TRAIL in combination with taxanes, such as paclitaxel or docetaxel on prostate cancer cells. We reported that co-treatment of prostate cancer cells with noncytotoxic concentration of taxanes significantly sensititizes prostate cancer cells to TRAIL induced cytotoxicity.
Conclusions. Paclitaxel or docetaxel markedly augmented TRAIL mediated cytotoxicity against prostate cancer in vitro. The obtained results suggest that combined treatment of TRAIL and taxanes may provide the basis for a new therapeutic approach to induce cytotoxicity in prostate cancer cells.