Adenoviral-p53 gene transfer to orthotopic and peritoneal murine bladder cancer.

Abstract

This study was designed to examine the potential for adenoviral-mediated gene therapy in primary and metastatic bladder cancer. Orthotopic and intraperitoneal bladder tumors were established after delivery of 1 x 10(6) MBT-2 cells into syngeneic mice. Gene transfer was accomplished via intravesical or intraperitoneal instillation by using an E-1 deleted adenovirus encoding LacZ or human p53. Successful tumor transduction was confirmed in tumor DNA and mRNA by polymerase chain reaction. Detection of recombinant gene product was detected by histochemical staining (X-gal) and Western blot. Palpable tumors developed 18 days following implantation. LacZ and p53 mRNA were present in tumor and adjacent normal tissue after bladder and intraperitoneal vector administration. Recombinant gene products were identified by histochemistry and Western blot. Bladder tumor-directed gene transfer using adenoviral vectors is an efficient and powerful tool for evaluating the adjuvant role of therapeutic gene products.