N/2/3DS 肝素抑制抑制小鼠黑色素瘤细胞B16F10转移

umor metastasis is a complicated, multi-step process. The formation of tumor cell-platelet emboli complexes in the blood stream is an essential step during metastatic process. In the process of the formation of “microthrombus”, plasma protein, adhesion molecules on the platelets, especially the selectin and integrin familys, play very important roles. Heparin is commonly used as an anti-coagulant in the clinic, and many studies indicated that heparin also inhibits tumor metastasis. However, heparin has not been widely used as an anti-metastasis agent in the clinic due to its side-effect (bleeding) to the patients. In the past, anti-metastasis effect of heparin was thought to correlate with its anti-coagulation activity, but some recent studies find its anti-metastasis effect doesn’t completely correlate with its anti-coagulation activity and other bioavailability of heparin may involve in. Some experiments indicate its anti-coagulation activity can be altered by chemical modification. Our experiment showed that the anti-coagulation ability of chemically modified heparins can be significantly reduced. In this study we analyzed the anti-coagulation activity and anti-metastasis effect of various chemically modified heparins. It is found that N/2/3DS heparin retain the inhibitory effect on tumor metastasis. Under shear stress condition, heparin and N/2/3DS heparin reduce the number of adhered B16F10 to platelets. Our experiments show that fibrinogen promotes the adhesion of B16F10 to platelets, and N/2/3DS heparin inhibits this effect. The results suggest that it is possible that N/2/3DS heparin can be used as anti-metastasis drug in clinic.