Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2

Wang,Zhiyu; Wang,Juan; Li,Xing; Xing,Lianping; Ding,Yan; Shi,Penghui; Zhang,Yuehua; Guo,Shenghu; Shu,Xin; Shan,Baoen

doi:10.3892/ijo.2014.2545

Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2

Authors:
- Zhiyu Wang
- Juan Wang
- Xing Li
- Lianping Xing
- Yan Ding
- Penghui Shi
- Yuehua Zhang
- Shenghu Guo
- Xin Shu
- Baoen Shan
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Affiliations: Department of Immunology and Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, University of Rochester School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA, Department of Pathology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Oncology, Armed Police General Hospital, Beijing 100039, P.R. China, Scientific Research Centre, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: July 17, 2014 https://doi.org/10.3892/ijo.2014.2545
Pages: 1469-1478

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Abstract

Prostate cancer is the most common malignancy diagnosed in males, and bone metastases remain a significant source of morbidity and mortality in this population. Ubiquitin ligase E3s and proteasomes were thought to play essential roles in the development of cancers, therefore, they were proposed as therapy targets for the treatment of solid and hematological malignancies. Bortezomib, well-known as a proteasome inhibitor, has been observed with exact anticancer effect both in cell and animal models for several solid tumor types, including prostate cancer. To explore activities of the ubiquitin ligase E3s WWP1, Smurf1 and Smurf2 in oncogenesis and bone metastasis of prostate cancer, as well as in the functional mechanism of bortezomib in preventing prostate cancer, transcription and expression levels of WWP1, Smurf1 and Smurf2 genes in cell lines or tissues of benign prostate hyperplasia and human prostate cancer with and without bone metastasis were tested. Moreover, human prostate cancer PC3 cell lines were treated with bortezomib at different concentration gradients and then their proliferation at different time points, mRNA and protein levels were investigated. The results indicated that transcription and expression levels of WWP1, Smurf1 and Smurf2 genes in prostate cancer without bone metastasis were significantly higher compared to those in benign prostate hyperplasia (P<0.05), whereas significantly lower than prostate cancer metastatic to bone (P<0.05). Furthermore, bortezomib reduced the transcription and expression levels of WWP1, Smurf1 and Smurf2 genes in prostate cancer cell lines in a dose-dependent manner, thus, inhibiting the proliferation of prostate cancer cells. Elevated transcription and expression levels of ubiquitin ligase E3s WWP1, Smurf1 and Smurf2 genes may be the mechanisms of occurrence, development and metastasis of prostate cancer. In addition, bortezomib can prevent prostate cancer and its bone metastasis by downregulating WWP1, Smurf1 and Smurf2.

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