Objective: To study the therapeutic potential of TRAIL and in combination with subtoxic level of chemotherapeutic agents in the treatment of human hepatocellular carcinomas (HCCs).
Methods: The plasmid pcDNA 3.0-hTRAIL was transfected into COS-7 cells, and it was transiently expressed. The cytotoxic functions of the expressed product and in combination with chemotherapeutic agents were detected.
Results: The transiently transfected COS-7 could express the active human TRAIL. It had mild cytotoxic functions on HCC cell lines. The cytotoxicity rates in both cell lines were 9.2% and 9.5% respectively. Chemotherapeutic agents, mitomycin (M), 5-FU and actinomycin D (AcD) dramatically augmented TRAIL induced cytotoxic function. There were significant differences in the cytotoxicity between the use of single agent and in combination with TRAIL (TRAIL + M, M; 60.1%, 32.6%, TRAIL + 5-FU, 5-FU: 68.1%, 29.2%, TRAIL + AcD, AcD; 72.9%, 58.6%) (P < 0.05).
Conclusions: The combination of human TRAIL and chemotherapeutic agents, such as mitomycin, 5-FU and actinomycin D, seemed to exert a synergistic effect compared with either agent alone, and it might have therapeutic potential in the treatment of human HCC.