[Inhibitory effect of NS398 on the proliferation of human ovarian cancer cell lines CAOV3 and OVCAR3 in vitro].
OBJECTIVE
To observe the inhibitive effect of cyclooxygenase-2 (COX-2) selective inhibitor, [N-[2-(cyclohexyloxy)-4-nitrophenyl]-methane sulfonamide] (NS398, one of nonsteroidal anti-inflammatory drugs), on human ovarian cancer cell lines CAOV3 and OVCAR3 during the proliferative process in vitro.


METHODS
Streptovidin peroxidase conjugated (SP) immunohistochemical assay was performed to examine the expression of COX-2 protein in human ovarian epithelial serous cancer cell lines CAOV3 and OVCAR3 respectively. The proliferative inhibition process of the two cell lines by NS398 was observed with methyl thiazolyl tetrazolium (MTT) rapid photocolorimetric assay. Cell morphologic changes were observed under the inverted phase contrast microscope and electron microscope. DNA ladder assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were employed for the cell apoptosis.


RESULTS
COX-2 protein was expressed in both of the cell lines. The inhibitory rate of proliferation exerted by NS398 increased with the density and the time of NS398 respectively. In contrast to the control, the absorbance of the experiment (NS398 200 micro mol/L for 72 h) decreased obviously (P < 0.05). With regard to the cell morphology, the "vacuole" presented in the cytoplasm and apoptosis body was able to be observed, and the microvilli on the surface of the cell disappeared. There were characteristic ladder bands after CAOV3 and OVCAR3 were treated by NS398 (100 micro mol/L) for 72 h. The brown-yellow granules located in the nucleus of most CAOV3 cells, which indicated apoptosis.


CONCLUSIONS
Above findings suggest that COX-2 may provide an effective chemotherapeutic target for ovarian cancer, and selective COX-2 inhibitors can be used as chemotherapeutic agents for ovarian cancer.
Wang
Chun-yan
CY
Department of Obstetrics and Gynecology, Second Affiliated Hospital, China Medical University, Shenyang 110001, China.
Wang
Min
M
Wang
Xin-yan
XY
Zhang
Shu-lan
SL
Wang
Yi-xun
YX
Li
Lian-kun
LK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide