Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C(57)Bl(6) mice with syngeneic melanoma B16

Purpose: The aim of the present study was to investigate the effect of a mi xture of proteolytic enzymes (comprising trypsin, chymotrypsin and papain) on the metastatic model of syngeneic melanoma B16. Methods: 140 C(57)Bl(6) mice were divided into two control and two "treated" groups. Control groups received saline rectally, twice a day starting 24 h after intracutaneous t ransplantation (Cl) or from the time point of the primary B16 melanoma exti rpation (C2), respectively. "Treated" groups were rectally administered a m ixture of 0.2 mg trypsin, 0.5 mg papain, and 0.2 mg chymo-trypsin twice dai ly starting 24 h after transplantation (E1) or after extirpation of the tum or (E2), respectively. Survival of mice and B16 melanoma generalization wer e observed for a period of 100 days. Immunological evaluation of B16 melano ma cells in the ascites was accomplished. CD44, CD54 and CD106 cells were m easured by flow cytometry. Results: Administration of proteolytic enzymes t o mice inhibited the growth of primary tumors, and tumor recurrences were l ess numerous. Importantly, metastasis was considerably curtailed both in th e vicinity of the primary tumor and at distant locales. These findings corr elated with a decreased expression of CD44 and CD54 molecules in tumors exp osed to proteolytic enzymes in vivo. Conclusions: Our data suggest that ser ine and cysteine proteinases suppress B16 melanoma, and restrict its metast atic dissemination in C(57)Bl(6) mice.