Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells
H. Matsuzaki et al., Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells, CLIN CANC R, 7(2), 2001, pp. 407-414
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel
member of the tumor necrosis factor superfamily of cytokines that induces c
ell death by apoptosis, TRAIL has been shown to be effective in almost two-
thirds of solid tumors tested thus far, but its effect on pancreatic cancer
cells is unknown. We tested the effect of TRAIL on seven human pancreatic
cancer cell lines (HPAF, Panel, Miapaca2 Bxpc3, Panc89, SW979, and Aspc1) i
n vitro. Of these cell lines, all but Aspc1 showed a significant dose-depen
dent increase in apoptosis, The apoptotic rate, as detected by a terminal d
eoxynucleotidyl transferase-mediated nick end labeling assay, was highest i
n Bxpc3 (71.5 %), followed by HPAF (38.0%), Miapaca2 (24.9%), Panel (16.1%)
, Panc89 (15.8%), SW979 (13.9%), and Aspc1 (5.2%). Multiple treatments were
more effective than a single treatment and caused a sustained and profound
cell death in all but Aspc1 cells. There was no correlation between the ef
fect of TRAIL and the differentiation grade of the cell lines, p53 mutation
, or bcl-2 or bax expression. The resistance of Aspc1 cells to TRAIL was no
t related to the lack of TRAIL receptors, The combination of actinomycin D
and TRAIL induced an almost complete lysis of Aspc1 cells, whereas actinomy
cin D alone had no effect on cell survival but inhibited the expression of
the Flice inhibitory protein, which is assumed to play a role in the apopto
tic pathway of TRAIL, Thus, the combination of actinomycin D and TRAIL appe
ars to be a promising approach for the therapy of pancreatic cancers resist
ant to TRAIL.