Journal of Practical Oncology ›› 2019, Vol. 33 ›› Issue (5): 407-414.doi: 10.11904/j.issn.1002-3070.2019.05.005

• Basic Research • Previous Articles     Next Articles

Astragalin inhibits hypoxia-induced proliferation and invasion of ovarian cancer cells by up-regulating PHD2

SONG Ling, FU Qiong   

  1. Department of Gynecology and Obstetrics,Chengdu Second People′s Hospital,Chengdu 610017,China
  • Published:2019-11-05

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Abstract: Objective The objective of this study was to explore the effect and mechanism of astragaline(ATG)on inhibition of HIF-1α,proliferation and invasion of ovarian cancer cells.Methods OVCAR-8 and SK-OV-3 cells were cultured in hypoxic conditions and treated with ATG(ATG group)or ATG combined with PHD2 inhibitor IOX2(ATG+IOX2 group)for 24h.The cells were just cultured in hypoxic condition for 24 h as a blank control.Western blot and real-time fluorescent quantitative PCR were used to detect the expression of HIF-1α,PHD2,PCNA,MMP-2 and MMP-9 at levels of mRNA and protein in each group.The cells cultured under normal conditions were used as a negative control,and the changes of hypoxic status in cells were detected after ATG treatment by hypoxia kit.Transwell assay was used to detect the invasive ability of cells in each group;CCK-8 kit was used to determine the activity of cell proliferation in each group.OVCAR-8 and SK-OV-3 cells were treated with gradient concentrations of ATG combined with gradient concentrations of carboplatin or cisplatin for 72h,the cell proliferation activity was detected by CCK-8 kit,and combined effect analysis was also performed.Results Under hypoxic conditions,compared with the blank control group,the expression of PHD2 at levels of protein and mRNA in the ATG group were increased,cell proliferation and invasion ability were decreased,and the expression of HIF-1α protein was decreased in OVCAR-8 and SK-OV-3 cells;the expression of PCNA,MMP-2 and MMP-9 at levels of protein and mRNA were decreased;but the expression of HIF-1α mRNA and cell hypoxia status did not change.When compared with the ATG group,the abilities of proliferation and invasion in the ATG+IOX2 group were increased in OVCAR-8 and SK-OV-3 cells;the expression of PCNA,MMP-2 and MMP-9 at levels of protein and mRNA as well as the expression of HIF-1α protein were increased,but the mRNA level of HIF-1α did not change.In addition,ATG could significantly enhance the sensitivity of OVCAR-8 and SK-OV-3 cells to cisplatin and carboplatin,and both combinations showed a good synergistic effect.Conclusion ATG can promote the degradation of HIF-1α by hypoxia via up-regulating PHD2 expression,resulting in inhibiting proliferation and invasion of ovarian cancer cells.

Key words: Astragaline, Ovarian cancer, Hypoxia, HIF-1α, Invasion

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