[Primary study of vasculogenic mimicry induced by hypoxia in epithelial ovarian carcinoma].
OBJECTIVE
To explore possibility of vasculogenic mimicry induced by hypoxia and the inhibitive effect by sirolimus in epithelial ovarian carcinoma in vitro.


METHODS
Based on three-dimensional cell culture system developed by Matrigel, ovarian cell lines SKOV3 and ES2 were induced under conditions of hypoxia, hypoxia added with sirolimus and no-hypoxia, respectively. Potential formation of tumor channels and their characterization of network were observed by light microscopy and scanning electronic microscopy. Relative hypoxia-inducible factor (HIF) 1alpha mRNA expression was detected by RT-PCR simultaneously.


RESULTS
The micrograph showed both SKOV3 and ES2 cells appeared expanded and re-shaped, then formed blood vessel-like structures such as cavity, channel, branch and network. These capabilities of cells were inhibited by sirolimus and no-hypoxia. The levels of HIF-1alpha mRNA expression of SKOV3 and ES2 were 0.801 +/- 0.034 and 0.736 +/- 0.059 under hypoxia, which were significantly higher than under hypoxia added with sirolimus (0.025 +/- 0.007, 0.231 +/- 0.035; P < 0.01, P < 0.05), and those under no-hypoxia (0.010 +/- 0.004, 0.011 +/- 0.002; both P < 0.01).


CONCLUSIONS
Hypoxia plays a key role in development of vasculogenic mimicry in epithelial ovarian carcinoma. Sirolimus can inhibit vasculogenic mimicry effectively by blocking HIF-1alpha at transcription level.
Yao
Liang-qing
LQ
Department of Gynecology, Obstetrics, Gynecology Hospital, Fudan University, Shanghai 200011, China.
Feng
You-ji
YJ
Ding
Jing-xin
JX
Xu
Cong-jian
CJ
Jin
Hong-yan
HY
Yin
Lian-hua
LH
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007797:Laminin; D008855:Microscopy, Electron, Scanning; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure; D011509:Proteoglycans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D020123:Sirolimus