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Article

TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells

  • Authors:
    • Yang Li
    • Danxi Zhu
    • Lidan Hou
    • Bin Hu
    • Min Xu
    • Xiangjun Meng
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, P.R. China, Department of Gastroenterology, School of Medicine, Shanghai Ninth People's Hospital of Shanghai Jiaotong University, Shanghai 200011, P.R. China, Department of Gastroenterology, Shanghai General Hospital of Shanghai Jiaotong University, Shanghai 200080, P.R. China
  • Pages: 1343-1349
    |
    Published online on: November 8, 2017
       https://doi.org/10.3892/ol.2017.7361
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Abstract

Tribbles homolog 3 (TRB3), a type of pseudokinase that contains a consensus serine/threonine kinase catalytic core structure, is upregulated in hepatocellular carcinoma. However, the effect of TRB3 expression in hepatocellular carcinoma and the molecular mechanisms underlying TRB3‑mediated effects on tumorigenesis in hepatocellular carcinoma have not been fully elucidated. The present study focused on the effect of TRB3 expression in MHCC97H hepatocellular carcinoma cells and investigated the underlying molecular mechanisms in MHCC97H cells. In the present study, it was revealed that TRB3 was significantly overexpressed in the MHCC97H hepatocellular carcinoma cell compared with L‑02 normal hepatic cells. Under endoplasmic reticulum (ER) stress induced by thapsigargin and tunicamycin, the levels of TRB3, CCAAT/enhancer binding protein homologous protein (CHOP), protein kinase B (AKT) and phosphorylated (p)AKT expression were upregulated. Furthermore, when the expression of TRB3 was silenced by short hairpin (sh)RNA, the survival of MHCC97H hepatocellular carcinoma cells was increased. Notably, following transduction with lentiviral containing TRB3‑shRNA, cell survival also increased after treatment with chemotherapy drug cisplatin. The present study demonstrated that knockdown of CHOP by shRNA was able to reduce TRB3 expression, and the knockdown of TRB3 markedly increased the level of pAKT. TRB3 was overexpressed in MHCC97H hepatocellular carcinoma cells, particularly under endoplasmic reticulum stress. Knockdown of TRB3 was able to increase cell survival. Therefore, TRB3 expression may induce apoptosis and reverse resistance to chemotherapy in MHCC97H hepatic carcinoma cells. The present study suggests that TRB3 is a key molecule that mediates the crosstalk between ER stress and AKT signal pathways. Furthermore, the present study may provide further insight into the cancer biology of hepatocellular carcinoma and the development of anticancer drugs targeting the ER stress and AKT signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Zhu D, Hou L, Hu B, Xu M and Meng X: TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncol Lett 15: 1343-1349, 2018.
APA
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., & Meng, X. (2018). TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncology Letters, 15, 1343-1349. https://doi.org/10.3892/ol.2017.7361
MLA
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., Meng, X."TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells". Oncology Letters 15.1 (2018): 1343-1349.
Chicago
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., Meng, X."TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells". Oncology Letters 15, no. 1 (2018): 1343-1349. https://doi.org/10.3892/ol.2017.7361
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Zhu D, Hou L, Hu B, Xu M and Meng X: TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncol Lett 15: 1343-1349, 2018.
APA
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., & Meng, X. (2018). TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncology Letters, 15, 1343-1349. https://doi.org/10.3892/ol.2017.7361
MLA
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., Meng, X."TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells". Oncology Letters 15.1 (2018): 1343-1349.
Chicago
Li, Y., Zhu, D., Hou, L., Hu, B., Xu, M., Meng, X."TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells". Oncology Letters 15, no. 1 (2018): 1343-1349. https://doi.org/10.3892/ol.2017.7361
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