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) prod uction and antitumor activity against human pancreatic cancer cells we re investigated. Lipid A (10 mglkg) 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 viab le cells. Activity of lipid A against transplanted human pancreatic ca ncer cells (MIA paca-2, Pane-1) was examined by determining tumor volu me, necrosis, and survival rate after intraperitoneal injections of li pid A (10 and 20 mg/kg) over 4 weeks. Serum TNF levels increased 80-fo ld in rats and 100-fold in mice after intravenous lipid A injection. A lthough specific tumor growth inhibition by lipid A was not observed i n vitro, tumor growth was significantly inhibited, and the survival ra te was improved in pancreatic cancer cell-transplanted nude mice treat ed 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 pancreat ic cancer are warranted.