Overcoming acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand by Bcl-XL small interfering RNA in human colon cancer
Zhu, H.-B.; Huang, X.-F.; Hu, J.-Z.; Zhou, W.; Chen, W.; Chen, L.-L.; He, C.
Zhonghua Zhong Liu Za Zhi 30(4): 245-249
2008
ISSN/ISBN: 0253-3766 PMID: 18788624 Document Number: 621907
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. 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. 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. 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.