Increased induction of apoptosis of human colorectal cancer cells after preoperative treatment with 5-fluorouracil

We examined whether the administration of 5-fluorouracil (5-FU) could enhance apoptosis of colorectal cancer cells, and we investigated the relationship between apoptosis and the expression of Ki-67, p53, and c-myc. Twenty patients with advanced colorectal cancer were divided into two groups. Ten received continuous intravenous 5-FU at 500 mg/body/day for 7 days preoperatively and 10 did not receive 5-FU and served as controls. Apoptotic cells were stained by so-called TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Apoptosis of cancer cells increased significantly to 18+/-6% in the 5-FU-treated group as compared to the controls (3+/-1%; p<0.001). Expression of Ki-67, a indicator of cell proliferation, was inversely correlated with the TUNEL staining that was specific for apoptosis and the percentage of cells immunostained for Ki-67 fell significantly to 34+/-14% of the apoptotic area as compared to 72+/-12% in controls (p<0.001). There was no clear correlation between expression of apoptosis and the expression of p53 or c-myc.