[Proliferation and apoptosis effect of rosiglitazone on human ovarian cancer cell line SKOV3].
OBJECTIVE
To study the effect of PPARgamma, activated by Rosiglitazone (RSG), on the regulation of cell cycle and apoptosis in human ovarian cancer cell line SKOV3.


METHODS
SKOV3 was treated with various levels of RSG (0.1, 1.0, 10 and 100 micromol/L), its proliferation was evaluated by MTT assay, apoptosis was determined by Hoechst33258 fluorescence and PI staining flow cytometry, and cell cycle analyzed by flow cytometry, respectively. The expression of PPARgamma, c-myc mRNA and protein were investigated by means of RT-PCR and immunocytochemistry respectively.


RESULTS
MTT assay indicated that RSG could inhibit the proliferation of SKOV3 in a concentration-dependent and time-dependent pattern. PI staining flow cytometry data demonstrated that the apoptosis of SKOV3 and cell cycle was arrested at G1 stage induced by RSG in a concentration-dependent manner, after 24h inducing with RSG at the concentration of 10, 100 micromol/L, the apoptosis rates were 45.75% and 51.97% respectively, which were significantly higher than that of control group. Hoechst33258 fluorescence staining demonstrated that the apoptosis bodies were found in the SKOV3 treated with RSG. RT-PCR and immunocytochemistry indicated human ovarian cancer SKOV3 cells expressed PPARgamma. PPARgamma mRNA and protein expression increased, while c-myc mRNA and protein expression decreased in SKOV3 cells treated with RSG after 24 h. (P < 0.05).


CONCLUSIONS
RSG significantly inhibits SKOV3 survival and induces its apoptosis by stoppage in G1 phase. The effect of growth inhibition is associated with downregulating expression of c-myc mRNA and protein via activation of PPARgamma.
Ren
Qian-chuan
QC
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Peng
Zhi-lan
ZL
Tan
Xin
X
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000473:pathology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D047495:PPAR gamma; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone