Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2008, Vol. 30 ›› Issue (6): 711-716.doi: 10.3881/j.issn.1000-503X.2008.06.017

• Original Articles • Previous Articles     Next Articles

Hypoxia Increases the Expression of Heparitinase and the Invasiveness through the Hypoxia Inducible Factor-1α Dependent Pathway in Human Ovarian Cancer Cell Line SKOV3

YUAN Cai-xia1;GU Shuang1;ZHANG Shu-hong2;ZHANG Xiang-ning1   

  1. 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China 2Department of Obstetrics and Gynecology, No.456 Hospital, People’s Liberation Army, Jinan 250031, China
  • Received:2008-03-06 Revised:1900-01-01 Online:2008-12-30 Published:2008-12-30
  • Contact: ZHANG Xiang-ning

Abstract: ABSTRACT: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-1α (HIF-1α). 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-1α and HPA. Cell invasiveness was measured by matrigel invasion assay. Results Western blotting showed that the expression of HIF-1α significantly increased compared with normoxic group(P<0.05). However, hypoxia had no obvious impact on HIF-1α 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-1α pathway, which plays an important role in the pathogenesis of ovarian cancer.

Key words: ovarian cancer, dypoxia inducible factor-1 α, deparitinase, rapamycin, invasiveness