Abstract: BACKGROUND ＆ AIM: To evaluate the mechanisms involved in acquiring the TRAIL drug-resistance gene in human colon cancer DLD1 cell line. MATERIAL AND METHODS: DLD1 cells were repeatedly treated with adenovirus-mediated TRAIL gene(Ad/gTRAIL), and DLD1-TRAIL/R cells resistant to Ad/gTRAIL were obtained. The cell growth was measured by MTT method. The expression of proteins involved in TRAIL-mediated apoptosis pathway was also showed by western blot analysis. Then the possible mechanisms involved in acquiring resistance were analyzed. RESULTS： DLD1-TRAIL/R cells resistant to TRAIL were obtained from TRAIL-sensitive DLD1 parent cells. But they were still sensitive to adenovirus-mediated Bax gene therapy. Further studies demonstrated that expression of Bcl-XL was dramatically increased whereas caspase-8 was significantly decreased in DLD1-TRAIL/R cells. Simultaneously, there was no cleaved caspase-8 found in the DLD1-TRAIL/R cells. CONCLUSION: After repeated treatment, DLD1 cells could acquire the specific resistance to TRAIL gene. The involved mechanisms may involve up-regulation of Bcl-XL and down-regulation of caspase-8.

Key words: TRAIL, gene therapy, resistance