Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway

  • Authors:
    • Jingyun Jin
    • Yonggang Guo
    • Yang Liu
    • Zhenguo Wang
    • Xiaosa Yang
    • Shengkai Sun
  • View Affiliations

  • Published online on: June 24, 2019     https://doi.org/10.3892/or.2019.7210
  • Pages: 1183-1193
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Abstract

Liver cancer is the fifth most commonly occurring cancer in men and the ninth most commonly occurring cancer in women, worldwide, and is associated with a high mortality rate. Sorafenib is a new inhibitor of multiple kinases, that is regarded as standard treatment for liver cancer. Human breast carcinoma metastasis‑suppressor 1 (BRMS1) is a tumor‑suppressor gene, that reduces the metastatic ability of tumor cells without affecting their tumorigenicity. In the present study, a model of BRMS1 overexpression and BRMS1 knockdown was established in HepG2 cells. The results revealed that the proliferation of HepG2 cells was inhibited in response to sorafenib treatment using MTT assay. Furthermore, BRMS1 overexpression enhanced the effect of sorafenib. In addition, expression of inflammatory response‑related genes was increased, while secretion of angiogenesis‑related molecules was decreased, and apoptosis was also activated after sorafenib treatment using qPCR method, and it was further demonstrated that this effect was mediated by inhibition of the PI3K/AKT/mTOR/ERK signaling pathway using western blot analysis. In conclusion, overexpression of BRMS1 potentiated the effect of sorafenib via PI3K/AKT/mTOR/ERK signaling, while knockdown of BRMS1 expression attenuated this effect. These findings may present a novel therapeutic strategy for liver cancer.
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September-2019
Volume 42 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Jin J, Guo Y, Liu Y, Wang Z, Yang X and Sun S: Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway. Oncol Rep 42: 1183-1193, 2019
APA
Jin, J., Guo, Y., Liu, Y., Wang, Z., Yang, X., & Sun, S. (2019). Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway. Oncology Reports, 42, 1183-1193. https://doi.org/10.3892/or.2019.7210
MLA
Jin, J., Guo, Y., Liu, Y., Wang, Z., Yang, X., Sun, S."Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway". Oncology Reports 42.3 (2019): 1183-1193.
Chicago
Jin, J., Guo, Y., Liu, Y., Wang, Z., Yang, X., Sun, S."Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway". Oncology Reports 42, no. 3 (2019): 1183-1193. https://doi.org/10.3892/or.2019.7210