INHIBITORS OF UROKINASE REDUCE SIZE OF PROSTATE-CANCER XENOGRAFTS IN SEVERE COMBINED IMMUNODEFICIENT MICE

Proteolytic enzymes are required to mediate tumor cell invasion and me tastasis. The urokinase plasminogen activator (uPA) is commonly overex pressed by many human cancers, Therefore, uPA is a logical target to i nhibit cancer invasion and metastasis. However, uPA inhibitors also re duce tumor growth, We used a mutated form of plasminogen activator inh ibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-a minobenzamidine and amiloride, known inhibitors of uPA, Our results sh ow that blocking uPA by uPA inhibitors reduces tumor size in experimen tal animals, Our molecular simulation of docking inhibitors to the uro kinase reveals that all tested small molecule inhibitors bind in proxi mity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors.