Therapeutic Effect on Targeted Hyaluronan Binding Peptide on Neurofibromatosis

摘要

To test our hypothesis that that the HA binding peptide (HABP/tachyplesin) may be a new antineurofibromatosis agent, the peptide were chemically synthesized in a large scale and its bioactivity on NF cells was examined and underlying mechanism was explored. The results showed that 1) HABP can significantly change the morphology of treated ST88-14 and STS26T NF cells and inhibit their proliferation or colony formation in a dose-dependent manner; 2) HA binding peptide binds to Bcl-2/Bcl-xL and induces apoptosis, which may be one of the mechanisms by which HABP inhibits ST88-14 and STS26T NF cells; 3) HA binding peptide is capable of reducing the level of phosphorylated ERK1; 4) HABP reduces the level of cell cycle related molecules, such as cyclin B1 and cdc 2; 5) HABP/tachyplesin binds to C1q on cell surface, activate the classical complement cascade, since it triggered several down-stream events including the cleavage and deposition of C4 and C3 and the formation of C5b-9 and destroy the integrity of tumor cells; 6) the HABP/tachyplesin exerts anti-tumor effect on NF cells both in vitro and in vivo. Since the HABP /tachyplesin is a simple biological peptide without any toxicity, it might have the potential to be used in anti-NF. It is worth to further pursue this project for developing a new agent to against the cell growth of neurofibromatosis.