ADENOVIRUS-MEDIATED P53 GENE-THERAPY IN NASOPHARYNGEAL CANCER

EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore t he potential use of adenovirus-mediated tumor suppressor p53 gene ther apy In NPC, we first examined the in vitro effects of p53 introduced i nto the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which reveal ed 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 line s, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-g alactosidase following Ad-LacZ infection using an MOI of 100, as compa red to 20-30% infectivity with the other NPC lines. Using RPMI 2650 ce lls injected into nude mice, we developed an animal model for nasophar yngeal 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. Objec tive 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.