OncoTargets and Therapy (2019-12-01)

Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells

  • Tong Y,
  • Tong K,
  • Zhu Q,
  • Wu Y,
  • Yang Y,
  • Zhang J,
  • Hu P,
  • Yan S

Journal volume & issue
Vol. Volume 12
pp. 10663 – 10670

Abstract

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Yaoyao Tong,1,2 Kun Tong,1,2 Qinghong Zhu,1 Yuqin Wu,3 Yi Yang,4 Jicai Zhang,1 Pei Hu,1,5 Shirong Yan2 1Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Central Operating Room, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 4Reproductive Medicine Centre, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 5Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of ChinaCorrespondence: Shirong YanHubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, No. 30, South Renmin Road, Maojian District, Shiyan City, Hubei Province, People’s Republic of ChinaEmail [email protected] HuDepartment of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Maojian District, Shiyan City, Hubei Province, People’s Republic of ChinaEmail [email protected]: To investigate the role of glypican-3 (GPC3) in cobalt chloride (CoCl2)-induced cell apoptosis in hepatocellular carcinoma.Methods: HepG2 cells were treated with CoCl2 in the absence or presence of GPC3 plasmid transfection. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. The expression of GPC3, hypoxia-inducible factor 1α (HIF-1α), c-myc, sp1, poly-ADP-ribose polymerase (PARP) and caspase-3 was determined by real-time PCR, Western blotting, and immunofluorescence after the cells were treated with different concentrations of CoCl2 or siRNA targeting HIF-1α.Results: CoCl2 significantly inhibited the proliferation of HepG2 cells and induced apoptosis. Additionally, the expression of GPC3 mRNA and protein was decreased, and overexpression of GPC3 attenuated the tumour inhibiting effects. Further studies showed that CoCl2 increased the expression of HIF-1α while reducing the expression of sp1 and c-myc; knockdown of HIF-1α elevated the expression of GPC3, sp1, and c-myc.Conclusion: CoCl2 inhibited the growth of HepG2 cells through downregulation of GPC3 expression via the HIF-1α/c-myc axis.Keywords: cobalt chloride, c-myc, glypican-3, hepatocellular carcinoma, hypoxia-inducible factor 1α

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