Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals

  • Authors:
    • Jingtao Zhong
    • Xiaoming Yu
    • Xiaofeng Dong
    • Hong Lu
    • Wuyuan Zhou
    • Lei Li
    • Zhongchao Li
    • Pengfei Sun
    • Xuetao Shi
  • View Affiliations

  • Published online on: February 6, 2018     https://doi.org/10.3892/ijmm.2018.3463
  • Pages: 2893-2900
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Abstract

Secretory clusterin (sCLU) is overexpressed in cancer and is associated with resistance to chemotherapy in several types of cancer, including hepatocellular carcinoma (HCC). Sorafenib (SOR), a multikinase inhibitor of Raf/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase (ERK) signaling and the receptor tyrosine kinase, is recognized as the standard therapeutic strategy for patients with advanced HCC. However, the role of sCLU in the resistance of HCC to SOR remains to be fully elucidated. In the present study, sCLU was silenced by CLU short hairpin (sh)RNA in Bel‑7402 and SMMC‑7721 cell lines, following which the cells were treated with SOR. Cell proliferation was determined using a CCK‑8 assay. Apoptosis was quantified using flow cytometry. The production of sCLU, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X sprotein and phosphorylated (p)ERK1/2 was analyzed using western blot analysis. The results showed that sCLU was overexpressed in three HCC cell lines. The downregulation of sCLU by CLU shRNA synergistically increased SOR sensitivity in the Bel‑7402 and SMMC‑7721 cells, and potentiated SOR‑induced cell apoptosis. In addition, silencing sCLU or combination with PD98059 decreased the SOR‑induced activation of pERK1/2. These findings indicate a novel treatment strategy for HCC.
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May-2018
Volume 41 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhong J, Yu X, Dong X, Lu H, Zhou W, Li L, Li Z, Sun P and Shi X: Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals. Int J Mol Med 41: 2893-2900, 2018
APA
Zhong, J., Yu, X., Dong, X., Lu, H., Zhou, W., Li, L. ... Shi, X. (2018). Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals. International Journal of Molecular Medicine, 41, 2893-2900. https://doi.org/10.3892/ijmm.2018.3463
MLA
Zhong, J., Yu, X., Dong, X., Lu, H., Zhou, W., Li, L., Li, Z., Sun, P., Shi, X."Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals". International Journal of Molecular Medicine 41.5 (2018): 2893-2900.
Chicago
Zhong, J., Yu, X., Dong, X., Lu, H., Zhou, W., Li, L., Li, Z., Sun, P., Shi, X."Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals". International Journal of Molecular Medicine 41, no. 5 (2018): 2893-2900. https://doi.org/10.3892/ijmm.2018.3463