Tumor growth suppression by adenovirus-mediated introduction of a cell growth suppressing gene tob in a pancreatic cancer model

Abstract

TOB (transducer of ErbB-2) is a tumor suppressor that interacts with protein-tyrosine kinase receptors, including ErbB-2. Introduction of the tob gene into NIH3T3 cells results in cell growth suppression. In this study, we evaluated the effect of tob expression in pancreatic cell lines (AsPC-1, BxPC-3, SOJ) and discuss the tumor-suppressing effects of adenoviral vector expressing tob cDNA. We first measured the levels of endogenous tob mRNA being expressed in all pancreatic cancer cell lines. Then, we examined the effect of adenoviral vector containing tob cDNA (Ad- tob vector) on cancer cell lines. The viral vector was expanded with transfection in 293 cells. The titer of the vector was 350 × 10 6 pfu/ml. These cancer cells were able to be transfected with MOI 20 without adenoviral toxicity. The transfection of Ad- tob vector results in growth suppression of SOJ and AsPC-1 cell lines. The magnitude of the expression of the Ad- tob gene in cancer is correlated to tumor suppressive activity. We prepared pancreatic cancer peritonitis models using a peritoneal injection of AsPC-1 cells. In this model, bloody ascites and multiple tumor nodules were seen at the mesentery after 16 days. AdCA tob (50 × 10 6 pfu/day) was administered from day 5 to day 9 after 4 days of peritoneal injection of 2 × 10 6 AsPC-1 cells. Tumor growth suppression occurred 10 days after peritoneal injection of AdCA tob compared with the control group. There were no tumor nodules in the abdomen and no bloody ascites. These results suggest that the peritoneal injection of AdCA tob has potential to suppress the formation of pancreatic cancer peritonitis, and can be applied for chemotherapy-resistant cancer peritonitis.