Antimetastatic effect of hepatotropic liposomal adriamycin on human metastatic liver tumors.
Adriamycin (ADM) was encapsulated in a galactose-conjugated hepatotropic liposome (hLip-ADM) and its ability to enhance the antitumor effect while reducing toxicity was compared with that of free ADM and a control Lip-ADM (cLip-ADM), in two in vitro animal models. Liver metastases were induced in rats by an intravenous injection of 8 x 10(6) AH-130 rat hepatoma tumor cells. All forms of the ADM completely inhibited liver metastasis when given at a dose of 5 mg/kg on day 14 after tumor implantation, whereas liver metastatic foci were observed in six of ten rats in the control group. The reduction in ADM toxicity by liposomalization was remarkable, as significant body weight loss was observed only in the free ADM group, in which four of ten rats died. Additional experiments utilized a human colon cancer xenograft (TK-4) to induce the growth of the liver metastases in mice by orthotopic implantation. The hLip-ADM completely inhibited liver metastasis in rats (0/11), whereas liver metastases developed in 10 of 12 mice in the control group and in 5 of 12 mice given cLip-ADM. Interestingly, liposomal ADM did not have a significant inhibitory effect on transplanted tumor growth assessed 6 weeks after transplantation. These findings indicate that hLip-ADM may be an effective strategy for inhibiting liver metastases from human colon cancer.
Matsuda
I
I
Department of Surgery II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Konno
H
H
Tanaka
T
T
Nakamura
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary*; D003110:Colonic Neoplasms / Q000473:pathology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009374:Neoplasms, Experimental; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D014183:Transplantation, Heterologous; D015431:Weight Loss
D000970:Antineoplastic Agents; D008081:Liposomes; D011956:Receptors, Cell Surface; C039707:galactose receptor; D004317:Doxorubicin