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Article

Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells

  • Authors:
    • Xiaoqing Wang
    • Zhihong Niu
    • Yang Jia
    • Meng Cui
    • Liping Han
    • Yongfei Zhang
    • Zheng Liu
    • Dongbin Bi
    • Shuai Liu
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Shandong University, Jinan, Shandong 250000, P.R. China, Department of Neurology, Shandong Police Hospital, Jinan, Shandong 250000, P.R. China, Department of Dermatology, Mount Qianfu Attached Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
  • Pages: 2121-2130
    |
    Published online on: February 3, 2016
       https://doi.org/10.3892/or.2016.4611
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Abstract

Prostate cancer is the second most frequently diagnosed cancer in males worldwide and is commonly associated with metastasis. Moreover, in prostate cancer, aminopeptidase N (APN) expression is closely correlated with metastasis. Ubenimex, an APN inhibitor, is widely used as an adjunct therapy for cancer, enhancing the function of immunocompetent cells and conferring antitumor effects. However, due to the low expression of APN, it is rarely used to treat prostate cancer. Recently, the induction of autophagy as a molecular mechanism has been strongly connected with tumor cell death. Thus, we investigated whether ubenimex could inhibit cell proliferation, migration and invasion by downregulating APN expression to induce autophagic cell death in prostate cancer cells. The LNCaP and PC-3 cell lines were treated with different doses of ubenimex. Cell viability was measured using growth curve analysis and WST-8 proliferation assay. Autophagic cell death was assessed using fluorescence microscopy and acridine orange/ethidium bromide (AO/EB) staining. Protein expression was assessed by immunofluorescence and western blot analyses. Autophagosomes were evaluated using transmission electron microscopy. Wound-healing migration assays were performed to determine the migratory ability of the PC-3 cells. In addition, nude mice were used in the present study to examine PC-3 cell proliferation in vivo. The results revealed that APN expression differed between the metastatic and non-metastatic prostate cancer cells. In addition, ubenimex inhibited APN expression in the prostate cancer cells. Ubenimex increased prostate cancer cell death, as determined using the lactate dehydrogenase (LDH) cytotoxicity assay. This effect was accompanied by increased levels of LC3B. Furthermore, ubenimex inhibited PC-3 cell proliferation in vivo and in vitro. Ubenimex inhibited the cell migration and invasion in prostate cancer cells by downregulating APN expression. Finally, ubenimex induced autophagic cell death in both metastatic and non-metastatic prostate cancer cells. Based on these results, ubenimex appears to be an excellent adjunctive therapy for the treatment of prostate cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Niu Z, Jia Y, Cui M, Han L, Zhang Y, Liu Z, Bi D and Liu S: Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. Oncol Rep 35: 2121-2130, 2016.
APA
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y. ... Liu, S. (2016). Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. Oncology Reports, 35, 2121-2130. https://doi.org/10.3892/or.2016.4611
MLA
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y., Liu, Z., Bi, D., Liu, S."Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells". Oncology Reports 35.4 (2016): 2121-2130.
Chicago
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y., Liu, Z., Bi, D., Liu, S."Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells". Oncology Reports 35, no. 4 (2016): 2121-2130. https://doi.org/10.3892/or.2016.4611
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Niu Z, Jia Y, Cui M, Han L, Zhang Y, Liu Z, Bi D and Liu S: Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. Oncol Rep 35: 2121-2130, 2016.
APA
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y. ... Liu, S. (2016). Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. Oncology Reports, 35, 2121-2130. https://doi.org/10.3892/or.2016.4611
MLA
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y., Liu, Z., Bi, D., Liu, S."Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells". Oncology Reports 35.4 (2016): 2121-2130.
Chicago
Wang, X., Niu, Z., Jia, Y., Cui, M., Han, L., Zhang, Y., Liu, Z., Bi, D., Liu, S."Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells". Oncology Reports 35, no. 4 (2016): 2121-2130. https://doi.org/10.3892/or.2016.4611
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