Deoxyribonuclease treatment prevents blood-borne liver metastasis of cutaneously transplanted tumour cells in mice

摘要

Murine L5178Y-ML cells, when transplanted subcutaneously into the flank of (BALB/c x DBA/2)F1 mice, grew locally and always formed spontaneous metastases in the liver. Even after surgical removal of the primary tumour mass 5 or 7 days after tumour cell inoculation, all mice died due to liver metastases within 18 days. Using this model of tumour metastasis, we examined whether serine protease or deoxyribonuclease I (DNase I) would affect metastasis. Spontaneous liver metastasis of L5178Y-ML cells was enhanced by systemic administration of alpha-chymotrypsin at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation. This result was consistent with a previous report on blood-borne lung metastasis. In contrast, systemic administration of DNase I at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation inhibited liver metastasis. Neither treatment affected primary tumour growth. An influence of DNase I on tumour cell arrest in the microvasculature of the liver was suggested by scanning electron microscopy. DNase I treatment resulted in a statistically significant prolongation of the survival period, however, the effect was not satisfactory. A more striking anti-metastatic treatment resulting in a greater prolongation of the survival period was achieved by combining surgical removal of the primary tumour mass with DNase I treatment. These results suggest that DNase I could be a potential therapeutic agent used in conjunction with surgery to prevent clinical blood-borne metastasis.