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Article

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

  • Authors:
    • Hao Zhang
    • Qingqing Wang
    • Jun Liu
    • Haoqiang Cao
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 314001, P.R. China
  • Pages: 9377-9384
    |
    Published online on: April 18, 2018
       https://doi.org/10.3892/ol.2018.8536
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Abstract

Long‑term sorafenib treatment triggers resistance to chemotherapy in patients with hepatocellular carcinoma (HCC). In order to investigate the mechanisms of sorafenib resistance in HCC, the aim of the present study was to develop a resistant human liver cell line via long‑term exposure to sorafenib. The cytotoxicity cell counting kit‑8 assay was used to evaluate drug sensitivity. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine the molecular mechanisms underpinning sorafenib resistance. Migratory and invasive properties in resistant cells were assessed using Transwell assays. The results from the present study revealed that resistant cells became insensitive to sorafenib treatment and exhibited increased migratory and invasive capacities. Activation of the phosphatidylinositol‑3‑kinase (PI3K)/Akt signaling pathway and epithelial‑mesenchymal transition was characteristic of resistant cells. The use of LY294002, a PI3K inhibitor, was able to suppress the activation of Akt and extracellular signal‑regulated kinase 1/2, attenuated the migratory and invasive capacities of resistant cells. Data from the present study indicates that inhibition of the PI3K signaling pathway with LY294002 exerts suppressive effects on sorafenib resistance and provides an attractive novel therapeutic regime in patients with advanced HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang H, Wang Q, Liu J and Cao H: Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma. Oncol Lett 15: 9377-9384, 2018.
APA
Zhang, H., Wang, Q., Liu, J., & Cao, H. (2018). Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma. Oncology Letters, 15, 9377-9384. https://doi.org/10.3892/ol.2018.8536
MLA
Zhang, H., Wang, Q., Liu, J., Cao, H."Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma". Oncology Letters 15.6 (2018): 9377-9384.
Chicago
Zhang, H., Wang, Q., Liu, J., Cao, H."Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma". Oncology Letters 15, no. 6 (2018): 9377-9384. https://doi.org/10.3892/ol.2018.8536
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang H, Wang Q, Liu J and Cao H: Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma. Oncol Lett 15: 9377-9384, 2018.
APA
Zhang, H., Wang, Q., Liu, J., & Cao, H. (2018). Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma. Oncology Letters, 15, 9377-9384. https://doi.org/10.3892/ol.2018.8536
MLA
Zhang, H., Wang, Q., Liu, J., Cao, H."Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma". Oncology Letters 15.6 (2018): 9377-9384.
Chicago
Zhang, H., Wang, Q., Liu, J., Cao, H."Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma". Oncology Letters 15, no. 6 (2018): 9377-9384. https://doi.org/10.3892/ol.2018.8536
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