Study Of The Factors Influencing The Stability Of TRAIL

Tumor necrosis factors (TNF)-related apoptosis-inducing ligand (TRAIL, also called Apo2L), is a new member of the tumor necrosis factor (TNF) family. Soluble form TRAIL induces apoptosis in a variety of human tumor cell lines but not in normal cells. So it has a good prospect to be used as a novel anticancer therapeutic agent. However, as a pharmaceutical protein, TRAIL is also instable. Here we studied factors affecting the stability of TRAIL.First of all, the effects of concentration of protein, NaCl and phosphate on the stability of TRAIL were studied. TRAIL protein degradation caused by biological and oxidative factors was also analysed.Then, the effects of pH and zinc ion on the trimerization of TRAIL were studied. The trimer TRAIL would aggregate mltimer under acidic conditions and dissociate monomer as the removal of Zinc. The effects of pH and zinc ion were reversible.In the end, the anticancer activity of TRAIL was studied by changing the content of the trimer. The results showed that, TRAIL trimer content is very important for the its anticancer activity. When trimer content increased from25.8%to74.9%, its anticancer activity increased correspondingly with ED50reducing from3.43×10-5mg/mL to1.06×10-5mg/mL.