[Enhanced induction of apoptosis of human colorectal cancer cells after preoperative treatment with 5-fluorouracil its relationship to DNA ploidy pattern].
We examined the relationship between apoptosis induced by 5-fluorouracil (5-FU) that was given preoperatively to colorectal cancer patients and DNA ploidy pattern, and investigated the cell cycle changes, and the expression of Ki-67. Twenty-nine patients with advanced colorectal cancer were divided into four groups, 3 days, 5 days, 7 days, and 10 days. Groups received continuous intravenous 5-FU at 500 mg/body/day preoperatively. Then, patients were divided into two groups by DNA ploidy pattern, diploid(D) and aneuploid(A). Apoptotic cells were stained by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of Ki-67 was examined by immunohistochemical staining. We used flow cytometry (FCM) for analysis of cell cycle distribution. Apoptosis of cancer cells was mostly increased in 7 days 5-FU administration in both D and A groups. The expression of Ki-67 was reduced according to the prolongation of the term of 5-FU administration in both D and A groups. We assessed S-phase fraction (SPF) to evaluate the cell cycle changes by 5-FU. Tumor samples of all patients after injection of 5-FU showed S-phase accumulation. The ratio of SPF (after 5-FU/before 5-FU) was the highest in the 5-day 5-FU administration group in both D and A groups. We concluded that apoptosis and S-phase accumulation were increased, and proliferative activity was decreased by preoperative 5-FU administration in colorectal cancer patients. However, there was no clear correlation between DNA ploidy pattern and these changes.
Yamane
N
N
First Dept. of Surgery, Faculty of Medicine, Tottori University.
Makino
M
M
Taniguchi
T
T
Kurayoshi
K
K
Kaibara
N
N
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D005472:Fluorouracil