The Effects Of Adinbitor, A Disintegrin From The Snake Venom Of Gloydius Brevicaudus, On Tumor Cells

Disintegrins are a kind of highly homologous polypeptide abstracted from snake venom, which contain an Arg-Gly-Asp (RGD) or Lys-Gly-Asp (KGD) sequence and plentiful cysteines, and the molecular weight is 5~9kD[1]. Most cellular integrins can recognize RGD sequence, while protein components of most extracellular matrix (ECM) contain RGD sequence. So disintegrins become the strong competitive antagonists to the binding of ECM and cellular integrins by force of the RGD recognition sequence and inhibit many physiological actions that the integrins participate in.Adinbitor, a disintegrin cloned from Gloydius brevicaudus , its scientific name is Agkistrodon halys brevicaudus stejneger venom in Lushun, China. As a novel disintegrin, Adinbitor is composed of 73 amino acid residues including 12 cysteine residues and an RGD three-peptide disintegrin characteristic recognition sequence and its relative molecular weight is 9kD. So it has the inhibitory effect on tumor as the strong antagonists to many integrin receptors.Tumorigenesis is a long-term and complicated process with many stages and by many elements, and its signal transduction system appears obvious defect. Integrins as a signal deliverer perform important function in the process. The research proves different integrin have different expression on tumor cells and perform different function in the different process of tumorigenesis. So integrins regulate the events such as tumor cells adhesion, proliferation, invasion and metastasis, apoptosis and the formation of tumoral blood vessel by delivering specific signal or inducing gene expression. Because all disintegrins contain an RGD distinctive recognition sequence which is essential for their biological activity and then become the strong antagonists to many integrin receptor by force of the sequence, they inhibit the function of integrins in the tumorigenesis. It has been found that disintegrins inhibit tumor cells adhesion to the fibronectin, vitronectin, laminin and collagens, and then inhibit tumor cells proliferation, invasion and metastasis and induce apoptosis.