Effects of a new synthetic lipid A on endogenous tumor necrosis factor production and antitumor activity against human pancreatic cancer cells.
The effects of a synthetic lipid A on tumor necrosis factor (TNF) production and antitumor activity against human pancreatic cancer cells were investigated. Lipid A (10 mg/kg) was injected into normal rats and mice and serum TNF levels were measured. Lipid A-induced inhibition of Molt 4 and MIA paca-2 cells in culture were measured by counting viable cells. Activity of lipid A against transplanted human pancreatic cancer cells (MIA paca-2, Panc-1) was examined by determining tumor volume, necrosis, and survival rate after intraperitoneal injections of lipid A (10 and 20 mg/kg) over 4 weeks. Serum TNF levels increased 80-fold in rats and 100-fold in mice after intravenous lipid A injection. Although specific tumor growth inhibition by lipid A was not observed in vitro, tumor growth was significantly inhibited, and the survival rate was improved in pancreatic cancer cell-transplanted nude mice treated with lipid A compared with controls. Synthetic lipid A induces TNF production and has antitumor activity against transplanted pancreatic cancer cells. Further studies of this lipid A as an agent for pancreatic cancer are warranted.
Satake
K
K
First Department of Surgery, Osaka City University Medical School, Japan.
Yokomatsu
H
H
Hiura
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D008050:Lipid A / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha