Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy.
OBJECTIVE
We tried to elucidate the effects of sulindac on human colorectal carcinoma.


METHODS
Sulindac (300 mg/day) was administered for two weeks before operation to 33 patients with sporadic colorectal carcinoma (Sulindac Group). Resected specimens were used to detect apoptosis by terminal dUTP nick end labeling and transforming growth factor (TGF)-beta1 expression by immunohistochemistry. The results were compared with those from the historical Control Group. Twenty-nine available preoperative biopsies taken from carcinomas before sulindac prescription and 22 concurrent colorectal adenomas (9 and 13 in Sulindac and Control Groups, respectively) in the resected specimen were also examined regarding TGF-beta1 expression.


RESULTS
In the resected carcinomas and adenomas, more frequent apoptosis and higher TGF-beta1 scores were observed in the Sulindac Group than in the Control Group. Overexpression of TGF-beta1 and apoptosis occurred in the same region in adenomas but not in carcinomas. A positive correlation between TGF-beta1 scores and apoptotic frequency was found in adenomas (P = 0.01, rho = 0.91) but not in carcinomas (P = 0.89, rho = 0.03).


CONCLUSIONS
We conclude that sulindac induces apoptosis in human colorectal carcinomas as well as in adenomas. Also, one of the antineoplastic effects of sulindac might be mediated by upregulating TGF-beta1 expression, particularly in colorectal adenomas.
Masunaga
R
R
Second Department of Surgery, Shimane Medical University, Izumo 693-8501, Japan.
Kohno
H
H
Dhar
D K
DK
Kotoh
T
T
Tabara
H
H
Tachibana
M
M
Kubota
H
H
Nagasue
N
N
D000236:Adenoma / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D013467:Sulindac / Q000008:administration & dosage / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013467:Sulindac