Tasanee PanichakulPakamas IntachoteAdisak WongkajorsilpBanchob SripaStitaya SirisinhaChulabhorn Research InstituteMahidol UniversityKhon Kaen University2018-08-202018-08-202006-01-01Anticancer Research. Vol.26, No.1 A (2006), 259-265025070052-s2.0-32144455416https://repository.li.mahidol.ac.th/handle/20.500.14594/23111Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) promotes apoptosis by binding to transmembrane receptors. It is known to induce apoptosis in a wide variety of cancer cells, but TRAIL-resistant cancers have also been documented. In this study, the relative resistance of human cholangiocarcinoma (CCA) cell lines against TRAIL-induced apoptosis is reported and the possible potential synergistic effect with triptolide, a diterpene triepoxide extracted from the Chinese herb Tripterygium wilfordii, in killing TRAIL-resistant CCA cells is investigated. Materials and Methods: Six human CCA cell lines were treated with various concentrations of TRAIL and the resistant cells were identified and subsequently tested for their sensitivity to a combination of TRAIL and triptolide. The susceptibility and resistance of the cells were based on analysis of cytotoxic and apoptotic induction and expression of anti-apoptotic factors (Mcl-1 and cFLIP). Results: The treatment of TRAIL induced a dose-dependent decrease in cell viability in 4 out of the 6 cell lines. A combination of TRAIL and triptolide enhanced cytotoxicity and apoptosis in these 2 resistant cell lines. The combined treatment enhanced activation of caspase-8 and its downstream signaling processes compared with the treatment with either one alone. Conclusion: The results presented show that human CCA cells were heterogeneous with respect to susceptibility to TRAIL-induced apoptosis. The combination of TRAIL and triptolide could enhance susceptibility to TRAIL-induced apoptotic killing in these TRAIL-resistant CCA cells, thus offering an alternative approach for the treatment of TRAIL-resistant cholangiocarcinoma.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS