Effect of Onconase ± Tamoxifen on ASPC-1 Human Pancreatic Tumors in Nude Mice

Abstract

To evaluate changes in tumor physiological parameters after treatment with ONCONASE (ONC), we used laser Doppler flowmetery for tumor blood flow (TBF) in legs of nude mice bearing AsPC-1 human pancreatic carcinoma. Tumor interstitial fluid pressure (TIFP) was measured using the wick-inneedle technique, while intratumoral pO₂ utilized O₂ sensitive needle electrodes. TBF was significantly increased by an i.p. injection of ONC, then returned to the untreated levels at 150 min post-treatment. Single and multiple intraperitoneal injections of ONC significantly reduced TIFP (post-treatment at 1–7 days). ONC significantly improved tumor oxygenation evidenced by an increase in median pO₂ from 4.2 mm Hg to 8.2 mm Hg. Since ONC had a synergistic interaction with tamoxifen (TAMX) on the cytotoxic clonogenicity of AsPC-1 tumor cells in vitro,we evaluated the antitumoral effects in vivo by ONC ± TAMX, using nude mice bearing AsPC-1 pancreatic tumor cells of ascite (intraperitoneally implanted) or solid (subcutaneously implanted to legs) tumors. ONC alone effectively retarded the tumor growth, but TAMX alone did not. ONC + TAMX was synergistically effective in inhibiting tumor growth.