[Effects of dihydroartiminisin on the adhesion, migration, and invasion of epithelial ovarian cancer cells].
OBJECTIVE
To investigate the effects of dihydroartiminisin (DHA) on the adhesion, migration, and invasion ovarian cancer cells.


METHODS
Human ovarian cancer cells of the lines SKOV3 and OVCAR3 were cultured. Suspensions of SKOV3 and OVCAR3 cells were treated with DHA of the concentrations of 0.5, 2.5, 12.5, and 62.5 micromol/L respectively, and then inoculated on the plate coated with Matrigel. MTT method was used to -determine the adhesion rate. Transwell membrane chamber model was used to evaluate the effect of DHA on the migration and invasion of the SKOV3 and OVCAR3 cells. Western blotting and reverse transcriptase polymerase chain reaction were used to detect the effect of DHA on the phosphorylation of focal adhesion kinase (FAK) and on the effect of expression of metal matrix proteinases (MMPs) and their tissue inhibitors (TIMPs) respectively.


RESULTS
(1) Compared to the cells without DHA treatment, the cell adhesion ability levels of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA decreased by 76.1% and 57.9% respectively (P < 0.05), while their migration ability levels decreased by 59.3% and 69.7% respectively (P < 0.05). (2) Both SKOV3 and OVCAR3 showed weak invasion ability, and DHA only showed a slight inhibitory effect on the cell invasion of these 2 lines (both P > 0.05). (3) Compared to the cells without DHA treatment, the phosphorylation level of FAK of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA decreased by 42.9% and 44.8% respectively (both P < 0.05). (4) RT-PCR showed mRNA expression of MMP2, TIMP1, and TIMP2, but not mRNA expression of MMP9 in both SKOV3 and OVCAR3 cells. The mRNA expression levels of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA increased by 1.5 and 2.6 times respectively (both P < 0.05).


CONCLUSIONS
DHA has inhibitory effects on the adhesion and migration of epithelial ovarian cancer cells, which may be related to its down-regulation of the phosphorylation of FAK in these cells.
Tan
Xian-Jie
XJ
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Lang
Jing-He
JH
Plouet
Jean
J
Wu
Ming
M
Shen
Keng
K
D017209:Apoptosis; D037621:Artemisinins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics
D037621:Artemisinins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; C039060:artenimol; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases