title: Effects of cyclooxygenase inhibitors in combination with taxol on expression of cyclin D1 and Ki-67 in a xenograft model of ovarian carcinoma.
abstract: The present study was designed to investigate the effects of cyclooxygenase (COX) inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone, 3 mg/kg SC-560 (a COX-1 selective inhibitor) alone by gavage twice a day, 20 mg/kg taxol alone by intraperitoneally (i.p.) once a week, or celecoxib/taxol, SC-560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test the mechanism of the combination treatment, the index of cell proliferation and expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. The mean tumor volume in the treated groups was significantly lower than control (p < 0.05), and in the three-drug combination group, tumor volume was reduced by 58.27% (p < 0.01); downregulated cell proliferation and cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01). This study suggests that the effects of COX selective inhibitors on the growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse xenograft model were similar to taxol. The three-drug combination showing a better decreasing tendency in growth-inhibitory effect during the experiment may have been caused by suppressing cyclin D1 expression.
authors.affiliation: Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Cai
authors.affiliation: Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
authors.forename: Yun-Xian
authors.initials: YX
authors.lastname: Tang
authors.affiliation: Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016861:Cyclooxygenase Inhibitors; D019394:Ki-67 Antigen; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D019938:Cyclin D1; D000068579:Celecoxib; D017239:Paclitaxel