Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide.
OBJECTIVE
To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide.


METHODS
Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 was measured by RT-PCR.


RESULTS
Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%+/-0.67%) was significantly higher than that in the control group (6.23%+/-1.29%, P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05).


CONCLUSIONS
Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.
Huang
Mao-tao
MT
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Chen
Zhi-xin
ZX
Wei
Bing
B
Zhang
Bo
B
Wang
Chun-hui
CH
Huang
Ming-hui
MH
Liu
Rui
R
Tang
Cheng-wei
CW
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage* / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology
D011720:Pyrazoles; D017481:Receptors, Somatostatin; D013449:Sulfonamides; C093733:somatostatin receptor 2; D000068579:Celecoxib; D015282:Octreotide