AB48. The effect of fluorouracil implants on orthopotic implantation nude mice with human gastric carcinoma cells

Objective: To explore the effect and mechanism of sustained release fluorouracil on orthopotic implantation nude mice with human gastric carcinoma cells.

Methods: Orthopotic implantation nude mice with human gastric carcinoma cells were established. Fluorouracil implants group (group A): Fluorouracil implants placed in or aside the tumor; 5-FU group (group B): 5-FU intraperitoneal injection into cavity of models; Control group (group C): given saline intraperitoneal injection. Nude mice were sacrificed after three weeks of intervention, and tumor weight and inhibitory rate were measured and calculated, flow cytometry was used to detect tumor cell apoptosis rate, expressions of MDR1, MRP-1, Fas were tested by RT-PCR.

Results: All models got tumors successfully. Tumor weight of group A was (1.25±0.15) g, group B (1.90±0.55) g, group C (2.25±0.21) g, and significant difference was found among 3 groups (P<0.05). Apoptosis rate of group A was higher than group B and group C (P<0.05). Levels of MDR1 mRNA in group A (2.83±0.44), group B (6.31±0.80) were both higher than that in group C (0.91±0.07), and level of MDR1 mRNA in group A were lower than in group B (all P<0.05). Levels of MRP1 mRNA in group A (3.04±0.39), group B (7.07±0.41) were both higher than that in group C (1.01±0.09), and level of MRP1 mRNA in group A were lower than in group B (all P<0.05). Levels of Fas mRNA in group A (3.51±0.64), group B (2.28±0.16) were both higher than that in group C (1.23±0.15), and level of MRP1 mRNA in group A were higher than in group B (all P<0.05).

Conclusions: Effect of fluorouracil implants was better than 5-FU, which leads to weaker MDR in tumor cells. And fluorouracil implants could promote apoptosis of tumor cell by up-regulating Fas.

Keywords: Sustained release fluorouracil; gastric cancer; orthopotic implantation nude mice; apoptosis; multidrug resistance