[Hypoxia increases the expression of heparitinase and the invasiveness through the hypoxia inducible factor-1alpha dependent pathway in human ovarian cancer cell line SKOV3].
OBJECTIVE
To investigate the heparitinase (HPA) expression and cell invasiveness in human ovarian cancer cell line SKOV3 during hypoxia, and explore their relationship with hypoxia inducible factor-1alpha (HIF-1alpha).


METHODS
SKOV3 cells were incubated with normoxia, hypoxia, and hypoxia plus rapamycin, respectively. SKOV3 cells of hypoxia group were incubated in 5% CO2 + 1% O2. Cells in hypoxia plus rapamycin group were incubated with 10 ng/ml of rapamycin before cultured under hypoxic condition. Cells in each group were collected for analysis after incubated with hypoxia for 12, 24, and 36 hours, respectively. Western blotting and RT-PCR were performed to detect the expressions of HIF-1alpha and HPA. Cell invasiveness was measured by matrigel invasion assay.


RESULTS
Western blotting showed that the expression of HIF-1alpha significantly increased compared with normoxic group (P < 0.05). However, hypoxia had no obvious impact on HIF-1alpha mRNA expression. The expressions of HPA protein and mRNA of SKOV3 cells of hypoxia group were significantly higher than normoxic group (P < 0.05). The up-regulation of HPA expression in hypoxic group decreased after the utilization of rapamycin. The cell invasion of hypoxic group was significantly higher than that of normoxic group (P < 0.05); meanwhile, the expression of HPA was positively correlated with the invasiveness of SKOV3 cells (r = 0.9863, P < 0.05).


CONCLUSIONS
Hypoxia may promote the expression of HPA and the invasiveness of SKOV3 cells through the HIF-1alpha pathway, which plays an important role in the pathogenesis of ovarian cancer.
Yuan
Cai-Xia
CX
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China.
Gu
Shuang
S
Zhang
Shu-Hong
SH
Zhang
Xiang-Ning
XN
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011133:Polysaccharide-Lyases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase