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

Molecular and Cellular Biochemistry
Yanli ZhangHongjuan Cui

Abstract

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 arr...Continue Reading

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Citations

May 31, 2017·Clinical and Experimental Pharmacology & Physiology·Qing OuyangLiang Yi
Oct 10, 2020·Molecular Oncology·Kei TakahashiKohei Miyazono
Aug 10, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jin LiuPatricia Forgez
Apr 28, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Tao HouXinmiao Liang

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