[Overcoming acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand by Bcl-XL small interfering RNA in human colon cancer].
OBJECTIVE
To investigate the reversing effect of Bcl-XL small interfering RNA (siRNA) on the acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in human colon cancer.


METHODS
Human colon cancer cells DLD1-TRAIL/R, with acquired resistance to TRAIL, were firstly transfected with Bcl-XL siRNA for 24 h followed by the treatment of TRAIL protein. The survival rate of DLD1-TRAIL/R cells was assessed by FACS analysis and cell number counting, respectively, and activation of its apoptotic signaling was evaluated by Western blot.


RESULTS
Bcl-XL siRNA effectively downregulated the expression of Bcl-XL protein and reversed the acquired resistance to TRAIL in DLD1-TRAIL/R cells. After combination treatment of Bcl-XL siRNA and TRAIL protein, the apoptotic rate of DLD1-TRAIL/R cells was more than 50% and survival rate was less than 40%, whereas there was no effect on the survival of DLD1-TRAIL/R cells after treatment with control treatment or TRAIL protein treatment alone (P < 0.05). Western blot analysis demonstrated that caspase-8, caspase-9, Bid, caspase-3, and poly (ADP-ribose) polymerase (PARP) were obviously activated after combination treatment with Bcl-XL siRNA and TRAIL protein, and the release of cytochrome C was also significantly increased.


CONCLUSIONS
Bcl-XL siRNA can effectively reverse the acquired resistance to TRAIL in human colon cancer cells, suggesting that it might be a new strategy for overcoming the resistance in cancer therapy.
Zhu
Hong-Bo
HB
Department of Colorectal Surgery and Biomedical Research Center, Sir Run Run Shaw Hospital, Hangzhou, 310016, China.
Huang
Xue-Feng
XF
Hu
Jing-Zi
JZ
Zhou
Wei
W
Chen
Wei
W
Chen
Lin-Lin
LL
He
Chao
C
D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
D051023:BH3 Interacting Domain Death Agonist Protein; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; D051020:bcl-X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases