Therapeutic effects of a new synthetic lipid A analog, ONO-4007, on rat hepatoma KDH-8 depend on tumor necrosis factor-sensitivity of the tumor cells.
ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. ONO-4007 was effective against KDH-8, a tumor necrosis factor (TNF)-sensitive rat hepatoma cell line, but neither effective against KMT-17, a TNF-resistant rat fibrosarcoma cell line, nor SST-2, a TNF-resistant rat mammary adenocarcinoma cell line. We have established two sublines from KDH-8 to further examine the therapeutic mechanisms of ONO-4007 in vivo: TNF-sensitive KDH-8/YK and TNF-resistant cKDH-8/11. The two sublines equally proliferated in vitro. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation. Although treatment with ONO-4007 had no effect on the growth of cKDH-8/11 in WKAH rats in vivo, 60% of KDH-8/YK-bearing rats treated with ONO-4007 survived. The administration of ONO-4007 brought about significant therapeutic effects on KDH-8/YK-bearing rats but not on cKDH-8/11-bearing rats. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
Kuramitsu
Y
Y
Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Matsushita
K
K
Ohiro
Y
Y
Obara
M
M
Kobayashi
M
M
Hosokawa
M
M
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D005260:Female; D007202:Indicators and Reagents; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D008050:Lipid A; C086889:ONO 4007; D014409:Tumor Necrosis Factor-alpha