Dihydroartiminisin inhibits the growth and metastasis of epithelial             ovarian cancer.
Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia             annua), has been utilised as an anti-malarial drug since ancient China. DHA has             also been shown to inhibit proliferation of cancer in vitro. However, the capacity             of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion,             invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined             following DHA treatment in vitro, using Matrigel coated plate, transwell membrane             chamber, and wound healing models, respectively. A mouse ovarian cancer model             was established by orthotopic inoculation of HO8910PM cell line in nude mice.             The growth and metastasis in vivo was determined 8 weeks post-implantation in             response to DHA treatment. The expression of phosphorylated focal adhesion kinase             (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western             blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages             were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell             proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner,             consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited             metastasis significantly in vivo, associated with reduced vWF expression and macrophage             infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in             part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration.
Department of Obstetrics and Gynecology, Ren-Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
Buchu
B
Wu
Ke
K
Hu
Shu
S
Li
Jing
J
Zhu
Liying
L
Gu
Haoran
H
Shen
Brett D
BD
Hambly
Shisan
S
Bao
Wen
W
Di
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D037621:Artemisinins; C039060:artenimol; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2