Recombinant sTRAIL induces cell death of tumor cell lines as well as primary cancer cells

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a new member of TNF family. It was reported that TRAIL could induce apoptosis of tumor cells but not normal cells in tissue culture system. To further s tudy the biological activity and potential clinical significance, a recombi nant soluble TRAIL (rsTRAIL) has been expressed stably in E. coil after tra nsformation of pET28b vector containing the extracellular domain of TRAIL. The yield of rsTRAIL is approximately as high as 60% of whole bacterial pro teins. The rsTRAIL, purified by Ni+-agarose affinity chromatography, could remarkably trigger apoptosis at the concentrations of 0.1-1 mu g/mL in all 7 tumor cell lines tested in vitro. However, this killing activity has not been observed in mouse fibroblast cell line (NIH3T3) as normal control. Fur ther investigation shows that the rsTRAIL could also kill primary tumor cel ls isolated freshly from patients with cardiac cancer, breast cancer and ma lignant thymoma, while the normal human peripheral blood lymphocytes are no t killed under the same conditions. These results provide new evidence that rsTRAIL could induce apoptosis of tumor cells specifically and it could be a new promising medicine for tumor therapy.