The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells.
OBJECTIVE
The p53 gene is considered one of the most important in the control of apoptosis, and its mutations have a close relationship with chemosensitivity. The aim of this work was to investigate the role of p53 in the apoptosis of colorectal cancer cells in vitro, induced by 5-fluorouracil (5-FU) and hydroxy-camptothecin (HCPT).


METHODS
A total of 39 colorectal cancer samples from patients were treated in vitro with 5-FU (10 microg/ml), 5-FU (10 microg/ml) + leucovorin (5 microg/ml), HCPT (0.1 microg/ml) and HCPT (0.1 microg/ml) + Salvia mitorrhiza (6 microl), using an in situ terminal deoxynucleotidyltransferase assay to detect chemosensitivity. p53 gene mutations from tumor DNA were detected, after amplification by the polymerase chain reaction of exons 5-8, by non-radioactive single-strand conformation polymorphism.


RESULTS
p53 gene mutations were observed in 43.6% (17/39) of colorectal carcinomas, when the terminal deoxynucleotidyltransferase assay was used to detect the tumor apoptotic rate. Cells with mutated p53 had lower chemosensitivity than those without (p < 0.01).


CONCLUSIONS
Routine assessment of p53 status may be helpful in selecting patients with the wildtype p53 gene, who have a predictably better response to chemotherapy.
Zheng
M
M
Department of Surgery, Rui Jin Hospital, Shanghai Second Medical University, P.R. China.
Wang
H
H
Zhang
H
H
Ou
Q
Q
Shen
B
B
Li
N
N
Yu
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
D000970:Antineoplastic Agents; C028098:10-hydroxycamptothecin; D005472:Fluorouracil; D002166:Camptothecin