OBJECTIVETo establish a 5-fluorouracil (5-FU)-resistant pancreatic adenocarcinoma (PAC) cell strain, and to investigate its biological characteristics.

METHODSThe PAC cell strain SW1990 was selected into a multidrug-resistant cell strain stepwise with 5-FU, one of the most common drugs used in PAC chemotherapy, for 12 months and subsequently named SW1990/FU. The cell strain was characterized in terms of morphology, biology, and cross-resistance to adriamycin(ADM), mitomycin-C (MMC), and gemcitabine. BHLB/c-m nude mice tumor growth and CEA and CA19-9 levels were analyzed. In addition, karyotyping and FACS analysis were performed in SW1990/FU and SW1990.

RESULTSThe SW1990/FU cell strain was 132.7 times more resistant to 5-FU than the parental SW1990 cells, and exhibited cross-resistance to other agents. Compared to the parental cells, SW1990/FU cells exhibited a smaller growth rate, delayed cell-doubling time, and specific changes in chromosomes 18. Tumor diameters in multidrug resistance and parental cells inoculated in in vivo experiments were (1.5 +/- 0.30) cm and (0.8 +/- 0.15) cm, respectively.

CONCLUSIONSMorphological adaptation and intracellular changes can be induced by drug challenge in PAC cells. SW1990/FU may be used as an experimental system for the search to overcome drug resistance and to elucidate possible mechanisms of acquired drug resistance in human pancreatic cancer.