In vitro and in vivo inhibitory effect evaluation of cyclooxygenase-2 inhibitors, antisense cyclooxygenase-2 cDNA, and their combination on the growth of human bladder cancer cells.
Overexpression of cyclooxygenase (COX)-2 is associated with the progression of various malignancies, but the contribution of COX-2 expression, bioactivity or their cooperation to bladder cancer growth calls for further clarification. In this study, we investigated the inhibitory effect of COX-2 inhibitors, antisense COX-2 nucleotide, and their combination on the growth of bladder cancer cells (5637, 5637-P and 5637-AS). Suppression of either COX-2 expression or activity caused reduced cell proliferation, enhanced cell numbers in G(1) phase, and increased apoptosis; the joint suppression of COX-2 expression and bioactivity enhanced the degree of cell growth inhibition. COX-2 antisense-expressing 5637-AS tumors showed a 41.42+/-3.08% growth inhibition as compared with 5637 controls. Oral administration of indomethacin (3mg/kg) or celecoxib (15 mg/kg) caused tumor growth inhibition by 31.5+/-14.87% or 83.17+/-1.17%, respectively. When COX-2 antisense cDNA and COX-2 inhibitor celecoxib were combined, the tumor growth inhibition rate was further increased up to 88.78+/-3.10%. These results provide evidence that celecoxib has potential therapeutic effect on bladder cancer, and the joint use of COX-2 antisense cDNA with celecoxib may improve their individual therapeutic effect, especially significantly increase the growth inhibitory effect of COX-2 antisense cDNA.
Qin
Jun
J
Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.
Yuan
Jianlin
J
Li
Ling
L
Liu
Heliang
H
Qin
Rongliang
R
Qin
Weijun
W
Chen
Baoqi
B
Wang
He
H
Wu
Kaichun
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D016373:DNA, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D018076:DNA, Complementary / Q000008:administration & dosage / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016373:DNA, Antisense; D018076:DNA, Complementary; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D007213:Indomethacin