[The effects of selective cyclooxygenase-2 inhibitors on the growth of gastric adenocarcinoma].
OBJECTIVE
This study was aimed to compare the effects of three kinds of selective cyclooxygenase-2 inhibitors (meloxicam, celecoxib, rofecoxib on the growth of gastric adenocarcinoma SGC7901 cell line, and to observe the effect of rofecoxib, on transplanted gastric cancer of nude mice in vivo.


METHODS
The proliferation and apoptosis of SGC7901 cells were measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end-labeling assay (TUNEL) separately. The expression of PCNA and COX-2 of gastric adenocarcinoma cells were detected by immunocytochemistry. Human gastric adenocarcinoma SGC7901 cells were implanted orthotopically in the stomach of nude mice. Rofecoxib (30 mg.kg-1.d-1) was administrated i.g. for eight weeks.


RESULTS
All the drugs potentially decreased 3H-thymidine incorporation into SGC7901 cells. The inhibition effects showed a dose-dependence manner. The median-response concentration was: 1.18 x 10(-7) mol/L (meloxicam), 1.68 x 10(-8) mol/L (celecoxib), 4.39 x 10(-9) mol/L (rofecoxib). After treatment with meloxicam, celecoxib, rofecoxib (1 x 10(-5) mol/L) for 24 hours, the apoptosis indices of SGC7901 cells were: 19.8% +/- 1.8%, 24.6% +/- 1.2% and 31.2% +/- 2.2%, respectively. The higher selective inhibition on COX-2, the higher apoptosis index (P < 0.01). Rofecoxib down-regulated the expression of COX-2 and PCNA of SGC7901 cell, both in vitro and in vivo. The inhibition rate for xenografts in situ in nude mice treated with rofecoxib was 93.9%.


CONCLUSIONS
The higher selective inhibition on COX-2, the stronger inhibition on gastric adenocarcinoma cells. Rofecoxib may be one of the important medicines in the treatment of gastric adenocarcinoma.
Liu
Chunlun
C
Department of Gastroenterology, First Hospital of Chongqing Medical University, Chongqing 400016, China.
Tang
Chengwei
C
Wan
Xuehong
X
Wang
Chunhui
C
Zhou
Xuchun
X
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011897:Random Allocation; D013274:Stomach Neoplasms / Q000473:pathology*; D013450:Sulfones; D014407:Tumor Cells, Cultured
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib