Induction of apoptosis in breast cancer cells by preoperative oral administration of 5-fluorouracil

We investigated whether 5-fluorouracil (5-FU) can induce apoptosis in breast cancer cells. Preoperatively, 23 breast cancer patients were divided into a group treated with 5-FU at 200 mg/day for 2 weeks (Group A) and a non-treatment group (Group B), and breast cancer tissues were taken postoperatively. DNA fragmentation by agarose electrophoresis and the TUNEL method were used to investigate the induction of apoptosis. The labeling rate with Ki-67 was measured to study the reproductive activity of tumor cells. The involvement of p53 in the apoptosis decision mechanism was also studied. DNA was more fragmented in Group A than in Group B. The apoptosis index by the TUNEL method was 1.88 +/- 1.03 in Group A, which was significantly higher than 0.36 +/- 0.86 in Group B. The labeling rate with Ki-67 was significantly higher in Group B(62.3 +/- 21.7) than in Group A (29.8 +/- 16.0). There was no difference in the protein expression of p53 regardless of the presence or absence of DNA fragmentation. These results indicate that 5-FU administration induces apoptosis in breast cancer cells and significantly inhibits their reproductive activity. Involvement of p53 in the apoptosis decision mechanism was not demonstrated.