AIM:There are conflicting data about p53 function on cellularsensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine thecombined effects of adenovirus-mediated wild-type (wt) p53gene transfer and 5-FU chemotherapy on pancreatic cancercells with different p53 gene status.METHODS:Human pancreatic cancer cell lines Capan-1~(p53mut),Capan-2~(p53wt),FAMPAC~(p53mut),PANC1~(p53mut),and rat pancreaticcancer cell lines AS~(p53wt) and DSL6A~(p53null) were used for in vitrostudies.Following infection with different ratios of Ad-p53-particles (MOI) in combination with 5-FU,proliferationof tumor cells and apoptosis were quantified by cellproliferation assay (WST-1) and FACS (PI-staining).Inaddition,DSL6A syngeneic pancreatic tumor cells wereinoculated subcutaneously in to Lewis rats for in vivo studies.Tumor size,apoptosis (TUNEL) and survival were determined.RESULTS:Ad-p53 gene transfer combined with 5-FUsignificantly inhibited tumor cell proliferation andsubstantially enhanced apoptosis in all four cell lines withan alteration in the p53 gene compared to those two celllines containing wt-p53.In vivo experiments showed themost effective tumor regression in animals treated withAd-p53 plus 5-FU.Both in vitro and in vivo analyses revealedthat a sublethal dose of Ad-p53 augmented the apoptoticresponse induced by 5-FU.CONCLUSION:Our results suggest that Ad-p53 maysynergistically enhance 5-FU-chemosensitivity most strikinglyin pancreatic cancer cells lacking p53 function.These findingsillustrate that the anticancer efficacy of this combinationtreatment is dependent on the p53 gene status of the targettumor cells. AIM: There are conflicting data about p53 function on cellularsensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type p53 gene transfer and 5 -FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS: Human pancreatic cancer cell lines Capan-1 ~ (p53mut), Capan-2 ~ (p53wt), FAMPAC ~ (p53mut), PANC1 ~ Cell lines AS ~ (p53wt) and DSL6A ~ (p53null) were used for in vitrostudies. Popular infection with different ratios of Ad-p53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cellproliferation assay (WST-1) and FACS (PI-staining). Adaptation, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size, apoptosis (TUNEL) and survival were determined .RESULTS: Ad-p53 gene transfer combined with 5-FUsignificantly inhibited tumor cell proliferation andsubstantially enhanced apoptosis in all four cell lines withan alteration in the p53 gene compared to those two celllines containing wt-p53. In vivo experiments showed themost effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyzes showed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION: Our results suggest that Ad-p53 maysynergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. The findings oflustrate that the anticancer efficacy of this combinationtreatment is dependent on the p53 gene status of the target tumor cells.