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
Dans Chinois
| WPRIM
| ID: wpr-259096
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>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Tumeurs de l'ovaire
/
Anatomopathologie
/
Polysaccharide-lyases
/
Transduction du signal
/
Hypoxie cellulaire
/
Régulation positive
/
Lignée cellulaire tumorale
/
Sous-unité alpha du facteur-1 induit par l'hypoxie
/
Génétique
/
Métabolisme
Limites du sujet:
Femelle
/
Humains
langue:
Chinois
Texte intégral:
Acta Academiae Medicinae Sinicae
Année:
2008
Type:
Article
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