论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
Authors Fan L, He Z, Head SA, Zhou Y, Lu T, Feng X, Zhang X, Zhang M, Dang Y, Jiang X, Wang M
Received 24 May 2018
Accepted for publication 31 July 2018
Published 23 October 2018 Volume 2018:10 Pages 4817—4829
DOI https://doi.org/10.2147/CMAR.S175256
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Background/Purpose: Prostate
cancer is a major burden on public health and a major cause of morbidity and
mortality among men worldwide. Drug combination therapy is known as a powerful
tool for the treatment of cancer. The aim of this study is to evaluate the
synergistic inhibitory mechanisms of clofoctol and sorafenib in the treatment
of prostate cancer. However, the molecular mechanisms of this phenomenon have
not been illuminated clearly. In this study, we investigated the anti-tumor
effects of clofoctol in combination with sorafenib in vitro and in vivo.
Methods: The
activity and mechanism of clofoctol in combination with sorafenib were examined
in PC-3cells. mRNA and protein expression of key players in the ER stress
pathway were detected with RT-PCR and Western blotting. Cell viability was
estimated by CCK-8 assay or Alamar blue assay, and apoptosis and cell cycle
were monitored and measured by flow cytometry. PC-3 cells were inoculated
subcutaneously in male BALB/c nude mice. The therapeutic regimen was initiated
when the tumor began showing signs of growth and treatment continued for 5
weeks.
Results: Our
data indicate that clofototol and sorafenib induce cell death through
synergistic induction of endoplasmic reticulum (ER) stress, resulting in
activation of the unfolded protein response (UPR). Combination therapy with
clofoctol and sorafenib induced an upregulation of markers of all three ER
stress pathways: PERK, IRE1 and ATF6. In addition, combination therapy with
clofoctol and sorafenib markedly inhibited the growth of prostate cancer
xenograft tumors, compared with clofoctol or sorafenib alone.
Conclusion: The
combination of clofoctol and sorafenib can serve as a novel clinical treatment
regimen, potentially enhancing antitumor efficacy in prostate cancer and
decreasing the dose and adverse effects of either clofoctol or sorafenib alone.
These results lay the foundation for subsequent research on this novel
therapeutic regimen in human prostate cancer.
Keywords: drug
combination, endoplasmic reticulum stress, unfolded protein response, prostate
cancer, clofoctol