title: Adenovirus-mediated p53 gene therapy in nasopharyngeal cancer.
abstract: EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore the potential use of adenovirus-mediated tumor suppressor p53 gene therapy In NPC, we first examined the in vitro effects of p53 introduced into the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which revealed that RPMI 2650 expresses wild-type p53 whereas Fadu and Detroit 562 encode mutant p53. Infection with p53-expressing adenovirus (Ad-p53) induced apoptosis and inhibited cell growth in all three NPC cell lines, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-galactosidase following Ad-LacZ infection using an MOI of 100, as compared to 20-30% infectivity with the other NPC lines. Using RPMI 2650 cells injected into nude mice, we developed an animal model for nasopharyngeal cancer. Established tumors (0.6-0.8 cm) were injected with 5x10(9) PFU Ad-LacZ, Ad-p53 or PBS in a 100 mu l volume. We found evidence for in vivo expression of beta-galactosidase or p53 and p21 up to two weeks following Ad-LacZ or Ad-p53 virus injection respectively. Objective regression of tumor size was observed at two weeks in 4/6 Ad-p53-treated tumors, but not in Ad-LacZ or PBS-treated tumors. The results provide an animal model for human nasopharyngeal cancer, and indicate a potential use of p53 in its therapy in vivo.
authors.affiliation: UNIV PENN,SCH MED,HOWARD HUGHES MED INST,CANC CTR,LAB MOL ONCOL & CELL CYCLE REGULAT,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,INST HUMAN GENE THERAPY,PHILADELPHIA,PA 19104.
authors.forename: Y
authors.initials: Y
authors.lastname: Zeng
authors.forename: N
authors.initials: N
authors.lastname: Prabhu
authors.forename: R
authors.initials: R
authors.lastname: Meng
authors.forename: W
authors.initials: W
authors.lastname: Eldeiry