Adenovirus-mediated small hairpin RNA targeting Bcl-XL as therapy for colon cancer

作者：Zhu, Hongbo; Zhu, Yuping; Hu, Jingzi; Hu, Wenxian; Liao, Yongqiang; Zhang, Jun; Wang, Da; Huang, Xuefeng; Fang, Bingliang^*; He, Chao

来源：International Journal of Cancer, 2007, 121(6): 1366-1372.

DOI：10.1002/ijc.22856

• adenovirus
• Bcl-XL
• RNA interference
• small hairpin RNA
• colon cancer

Bcl-XL, an anti-apoptotic protein of Bcl-2 family, is overexpressed in colon cancers. To determine Bcl-XL's potential feasibility as a therapeutic target, we constructed a recombinant adenovirus that expressed a U6 promoter-driven small hairpin RNA (shRNA) targeting Bcl-XL (Ad/Bcl-XL shRNA) and evaluated the vector's ability to induce RNA interference in vivo and alter apoptosis induction in colon cancer cells and tumours. Ad/Bcl-XL shRNA effectively knocked down Bcl-XL expression in colon cancer cells and decreased their viability. Treatment with Ad/Bcl-XL shRNA but not control vectors led to dramatically increased cleavage of cellular apoptosis-related enzymes caspase-9, caspase-3 and poly (ADP-ribose) polymerase. Ad/Bcl-XL shRNA also significantly suppressed the growth of subcutaneous tumours derived from DLD1 cells in a nude mouse model and did so without causing any obvious damage to normal tissues or normal human fibroblasts. Together, our results support the feasibility of using adenovirus-mediated RNA interference therapy targeting Bcl-XL against colon cancers and warrant further studies of its safety and efficacy.

• 出版日期2007-9-15
• 单位浙江大学