Tumor Biology

, Volume 36, Issue 3, pp 2143–2153 | Cite as

NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways

Research Article


The purposes of this study are to investigate the antitumor activities of NSK-01105, a novel sorafenib derivative, in in vitro and in vivo models, and explore the potential mechanisms. The effects of NSK-01105 on proliferation and apoptosis of prostate cancer cells were established by cytotoxicity assays, apoptosis analysis, flow cytometry analysis, and Western blot analysis. Two xenograft tumor models were used to verify the therapeutic effect of NSK-01105 in vivo. NSK-01105 exhibited broad-spectrum antitumor activity, particularly in prostate cancer cells. Characterization of apoptosis morphology was observed, and the percentage of apoptosis-positive cells significantly increased after NSK-01105 treatment for 24 h. Furthermore, a significant increase of the “sub-G1” population in LNCaP and PC-3 cells after NSK-01105 treatment was determined by cell cycle analysis. Tumor growth was significantly suppressed by once daily oral 30 mg/kg dose of NSK-01105 with the inhibition rates of 63.82 % in LNCaP models and 64.29 % in PC-3 models, respectively. The activation of Raf-1 kinase and epidermal growth factor receptor was downregulated by NSK-01105 at 10 μmol/L. Consequently, the dual inhibitions of Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways were observed by Western blot analysis. Collectively, our results suggest a role of NSK-01105 in treatment for human prostate tumors by inhibiting cell proliferation and inducing apoptosis. NSK-01105 appears to be a promising orally active anticancer drug and deserves further investigation.


Apoptosis analysis Raf/MEK/ERK pathway PI3K/Akt/mTOR pathway EGFR inhibitor 



This research was supported by the National Basic Research Program of China (No. 2012CB724003) and National Natural Science Foundation of China (No. 81202038).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Pengfei Yu
    • 1
  • Liang Ye
    • 2
    • 4
  • Hongbo Wang
    • 2
    • 3
  • Guangying Du
    • 2
    • 3
  • Jianzhao Zhang
    • 2
  • Jinghai Zhang
    • 1
  • Jingwei Tian
    • 2
    • 3
  1. 1.School of Life Science and Bio-pharmaceuticsShenyang Pharmaceutical UniversityShenyangChina
  2. 2.State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research DepartmentLuye Pharma Group LtdYantaiChina
  3. 3.School of PharmacyYantai UniversityYantaiChina
  4. 4.School of Pharmaceutical Sciences and Institute of Material MedicalBinzhou Medical UniversityYantaiChina

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