JOURNAL ARTICLE

[Overcoming acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand by Bcl-XL small interfering RNA in human colon cancer]

Hong-Bo Zhu, Xue-Feng Huang, Jing-Zi Hu, Wei Zhou, Wei Chen, Lin-Lin Chen, Chao He
Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology] 2008, 30 (4): 245-9
18788624

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.

CONCLUSION: 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.

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