Hypoxia increases the expression of heparitinase and the invasiveness through the hypoxia inducible factor-1alpha dependent pathway in human ovarian cancer cell line SKOV3 / 中国医学科学院学报
Acta Academiae Medicinae Sinicae
; (6): 711-716, 2008.
Article
in Zh
| WPRIM
| ID: wpr-259096
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>
Full text:
1
Index:
WPRIM
Main subject:
Ovarian Neoplasms
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Pathology
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Polysaccharide-Lyases
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Signal Transduction
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Cell Hypoxia
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Up-Regulation
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Cell Line, Tumor
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Hypoxia-Inducible Factor 1, alpha Subunit
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Genetics
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Metabolism
Limits:
Female
/
Humans
Language:
Zh
Journal:
Acta Academiae Medicinae Sinicae
Year:
2008
Type:
Article