Overcoming acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand by Bcl-XL small interfering RNA in human colon cancer.
- Author:
Hong-Bo ZHU
1
;
Xue-Feng HUANG
;
Jing-Zi HU
;
Wei ZHOU
;
Wei CHEN
;
Lin-Lin CHEN
;
Chao HE
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; BH3 Interacting Domain Death Agonist Protein; metabolism; Caspase 3; metabolism; Caspase 8; metabolism; Caspase 9; metabolism; Caspases; metabolism; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; metabolism; pathology; Cytochromes c; metabolism; Drug Resistance, Neoplasm; Humans; Poly(ADP-ribose) Polymerases; metabolism; RNA, Small Interfering; TNF-Related Apoptosis-Inducing Ligand; genetics; metabolism; Transfection; bcl-X Protein; genetics; metabolism
- From: Chinese Journal of Oncology 2008;30(4):245-249
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSHuman 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.
RESULTSBcl-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.
CONCLUSIONBcl-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.
