[The growth inhibitory effect of non-steroid anti-inflammatory drugs on ovarian cancer].
OBJECTIVE
To evaluate the effects of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) Celecoxib and Aspirin on the SKOV3 cell growth, apoptosis and neoplasm genesis of ovarian cancer in vitro and vivo.


METHODS
The proliferation of SKOV3 cells were determined by MTT assay, the apoptosis of cell were measured by flow cytometry (FCM), and the cell morphologic changes were observed under inverted phase contrast microscope. Xenografted nude mice models of human ovarian cancer were established, and then randomly allocated to treatment or control group, which was administered with either Celecoxib at the dosage of 10, 25, 50 mg/kg or distilled water alone (control) orally daily for 56 d. The mice weight, tumor volume and drug side effects were detected.


RESULTS
A dose-dependent inhibition of proliferation of SKOV3 cell appeared after Celecoxib or Aspirin administered for 24 h, and Celecoxib had more inhibiting efficiency to cell growth than Aspirin did. The inhibitory concentration 50% (IC50) in this assay for Celecoxib was 5X 10(-5) mol/L,whereas for Aspirin was 7X 10(-3) mol/L. With cell morphology the "vacuole" presented in the cytoplasm. In contrast to the control, the apoptotic rates (47. 1% and 15. 7%) of SKOV3 were increased after treatment with Celecoxib (5 X 10(-5) mol/L) and Aspirin(7 X 10(-3) mol/L). In nude mice, the average volume of tumor from control mice was (3. 283+/- 0. 432) cm(3) as compared with (2. 457+/- 0. 224) cm(3), (2. 198+/- 0. 500) cm(3), (2. 017+/-0. 166) cm' from Celecoxib mice (10, 25, 50 mg/kg), P<0. 05, and the rates of tumor growth inhibited by 3 Celecoxib dosages to SKOV3 cell burden mice were 25. 20%, 33. 00% and 38. 60%, in a dose-and time-dependent manner, and histopathologic examinations of kidney, liver, stomach and bowel showed no abnormality, with implying no untoward side effects.


CONCLUSIONS
Both COX-2 specific inhibitor Celecoxib and non-selective inhibitor Aspirin can potentially inhibit the tumor growth and induce apoptosis of SKOV3 cells, and the effect of Celecoxib is more potential than that of Aspirin.
Wang
Hong-jing
HJ
Department of Pathology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Peng
Zhi-lan
ZL
Liu
Xiao-qing
XQ
Yang
Kai-xuan
KX
Lou
Jiang-yan
JY
Luo
Feng-ming
FM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D001241:Aspirin