RT Journal Article
SR Electronic
T1 Triptolide Sensitizes Resistant Cholangiocarcinoma Cells to TRAIL-induced Apoptosis
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 259
OP 265
VO 26
IS 1A
A1 TASANEE PANICHAKUL
A1 PAKAMAS INTACHOTE
A1 ADISAK WONGKAJORSILP
A1 BANCHOB SRIPA
A1 STITAYA SIRISINHA
YR 2006
UL http://ar.iiarjournals.org/content/26/1A/259.abstract
AB Background: 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. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved