Molecular and Cellular Biochemistry

, Volume 389, Issue 1–2, pp 1–8 | Cite as

Neurotensin receptor1 antagonist SR48692 reduces proliferation by inducing apoptosis and cell cycle arrest in melanoma cells

  • Yanli Zhang
  • Shunqin Zhu
  • Liang Yi
  • Yaling Liu
  • Hongjuan Cui


Malignant melanoma is highly aggressive, and always resistant to conventional chemo-radiotherapy, which results in poor prognosis. As a specific antagonist of neurotensin receptor 1 (NTSR1), emerging evidences confirmed that SR48692 can reverse the pro-growth effect of neurotensin (NTS) by interrupting the interaction between NTS and NTSR1. A375 melanoma cell line was used in this experiment, and SR48692 was employed as the inhibitor of NTS/NTSR1 pathway. We detected the expression of NTSR1 by NTSR1 immunofluorescence and Western blot. After SR48692 treatment, cell proliferation was determined by cell counting, MTT assay and BrdU incorporation study, the cell cycle and apoptosis were performed by flow cytometry. At last Soft Agar Clonogenic assay and xenograft cancer mice model in vivo were used to confirm our result. In this study, we showed that NTSR1 is commonly high expressed in melanoma cells, but low expressed in normal immortalized human keratinocyte line HaCaT. SR48692 not only reduced cell proliferation and self-renewal potential in vitro, but also inhibited the tumor growth derived from A375 cells in NOD/SCID mice in vivo. Further, we originally reported that SR48692 inhibited cell proliferation through cell cycle arrest and apoptosis. Considering the favorable toxicity profile in vitro and in vivo though targeting NTS/NTSR1, SR48692 is worthy of further study and exploitation in melanoma treatment.


Malignant melanoma Neurotensin NTSR1 SR48692 Cell proliferation Apoptosis Cell cycle 



Malignant melanoma




Neurotensin receptor 1


Fetal bovine serum




Propidium iodide


Phosphate-buffered saline


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide



This study was supported by the National Basic Research Program of China (No. 2012cb114603), the National Natural Science Foundation of China (No. 31271462, 31172268, 81201551).

Disclosure of interest

The authors declare no conflict of proprietary, commercial, or financial interest in the products or companies described in this article.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yanli Zhang
    • 1
  • Shunqin Zhu
    • 2
  • Liang Yi
    • 3
  • Yaling Liu
    • 1
  • Hongjuan Cui
    • 4
  1. 1.Department of Dermatologythe Third Hospital of Hebei Medical UniversityShijiazhuangChina
  2. 2.Department of Life ScienceSouthwest UniversityChongqingChina
  3. 3.Neurosurgery Department, Daping Hospitalthe Third Military Medical UniversityChongqingChina
  4. 4.State Key Laboratory of Silkworm Genome BiologySouthwest UniversityChongqingChina

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