[Hypoxia increases the expression of heparitinase and the invasiveness through the hypoxia inducible factor-1alpha dependent pathway in human ovarian cancer cell line SKOV3]

Cai-Xia Yuan, Shuang Gu, Shu-Hong Zhang, Xiang-Ning Zhang
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae 2008, 30 (6): 711-6

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).

CONCLUSION: 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.

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