Antisense oligonucleotides to gastrin inhibit growth of human pancreatic cancer

Human pancreatic cancer is stimulated by the autocrine production of gastri n. In this study, the effects of administration of antisense oligonucleotid es to gastrin on growth of pancreatic cancer were evaluated in vitro and in vivo. Log phase BxPC-3 human pancreatic cancer cells in culture were expos ed to increasing concentrations (0.5-10 mu M) of a synthetic 20-mer antisen se phosphorothioate oligonucleotide to gastrin for 48 h and growth was asse ssed by the cellular proliferation assay. Growth was inhibited up to 88% by anti-gastrin oligonucleotides in a dose-related fashion compared to cells treated with diluent or a randomized sequence with the same composition as the anti-gastrin oligonucleotide. In vivo nude mice hearing BxPC-3 xenograf ts were treated daily for 14 days with a 0.1-ml intratumoral injection of e ither anti-gastrin (5 mu M), the scrambled sequence control phosphorothioat e oligonucleotide (5 mu M), or buffer. Tumors from the anti-gastrin-treated mice were significantly smaller in volume and weight and had less gastrin detected by radioimmunoassay than either controls. These results support th e role of gastrin as a stimulatory peptide for growth of human pancreatic c ancer. Antisense oligonucleotide to gastrin may have a role in the future t reatment of patients with pancreatic cancer. (C) 1999 Elsevier Science Irel and Ltd. AU rights reserved.