ANTIFUMOR EFFECT OF OLIGONUCLEOTIDE ENTLRAPPED-LIPOSOMES AGAINST THE DIGESTRE ORGAN CANCER.

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1. We established the liver metastatic model of human colon cancer strains, TK-3, -4, -6, -9, -10, -13 by using orthotopical transplantation, in which liver metastatic rate was from 38% to 83%. The point mutation of p53 was observed in TK-4 and the deletion of p53 was observed in TK-13. We could establish the stable liver metastatic model, because liver metastatic lesions, which were considered to have high malignant potential, were used for initial establisjhment of the 6 strains.2. Hepatotropic liposomes were prepared to enhance the uptake of entrapped genes into liver. To investigate the usefulness of hepatotropic liposomes, adriamycin (ADM) instead of p53 genes was entrapped in to liposomes (hLip-ADM). ADM concentration of the liver after the administration of hLip-ADM was significantly higher than that after administration of free ADM (unentrapped ADM) or cLip-ADM {ADM entrapped in control (non-hepatotropic) liposome}. Regarding the therapeutic effect, the administration of cLip-ADM decreased the liver metastasis to 42.9% and hLip-ADM inhibited the liver metastasis of TK-4 completely, whereas liver metastasis developed in 85.7% of the control after orthotopical transplantation.3. We have been tried to prepare the liposomes entrapped the human wild type p53 plasmid, instead of nucreotides, based on the results of our preliminary experiments and the studies reported recently. The human wild type p53 plasmid could be prepared by using pRC/CMV as the vector. However, we can not show the therapeutic effect of hLip-p53 (wild type p53 entrapped in hepatotropic liposome) on liver metastasis, so far. Antiproliferative effect and antimetastatic effect of hLip-p53 will be examined in the in vitro and in vivo experiments.