Inhibition of metastatic carcinoma cell growth in livers by poly(I):poly(C)/cationic liposome complex (LIC).
The complex of poly(I):poly(C) and a new cationic liposome (LIC) has a potent antitumor activity against many tumor cell lines in vitro, whereas poly(I):poly(C) itself has no such activity. In the present study we tested the sensitivity of 21 human colon and pancreatic cancer cell lines to LIC or Adriamycin in vitro. The growth of most of the cell lines was strongly inhibited by both LIC and Adriamycin in vitro, although a few insensitive cell lines were different. We also studied the in vivo antitumor activity of LIC or Adriamycin in three experimental liver metastasis models in nude mice using a human pancreatic cancer cell line (AsPC-1) and two human colon cancer cell lines (Ls174T and HCC-M1544). The administration of LIC or Adriamycin was started 3 days after the injection of tumor cells. Animals received 0.1 mg/kg LIC IV twice weekly or 5 mg/kg Adriamycin IV every 5 days during the experiments. LIC showed potent antitumor activity in all three liver cancer models. Although Adriamycin had potent antitumor activity in the HCC-M1544 model, it had only a moderate effect in the AsPC-1 model and at most a weak effect in the Ls174T model. At the effective doses LIC did not cause detectable pathological changes in the liver and did not elicit toxicity to mice in these models, whereas Adriamycin did exhibit toxic effects. These results suggest that LIC is a promising candidate drug to treat hepatic metastasis.
Hirabayashi
K
K
Discovery Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan. k.hirabayashi@po.nippon-shinyaku.co.jp
Yano
J
J
Takesue
H
H
Fujiwara
N
N
Irimura
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000627:therapeutic use*; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007369:Interferon Inducers / Q000627:therapeutic use*; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011070:Poly I-C / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007369:Interferon Inducers; D008081:Liposomes; D004317:Doxorubicin; D011070:Poly I-C