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Article

Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma

  • Authors:
    • Yicheng Chen
    • Huan Wang
    • Yuanlei Chen
    • Mingchao Wang
    • Guoqing Ding
    • Tao Li
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Sir Run‑Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, School of Medicine, Hunan Normal University, Changsha, Hunan 410081, P.R. China
  • Pages: 2039-2048
    |
    Published online on: August 28, 2019
       https://doi.org/10.3892/or.2019.7296
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Abstract

The clinical treatment of renal cell carcinoma (RCC) remains a major challenge. A number of novel agents and therapeutic strategies are currently undergoing active investigation. In the present study, we investigated the potential of GNF‑5837, a Trk inhibitor, in the treatment of RCC. Tropomyosin‑related kinases (Trk), a family of neurotrophin receptors, are vital for neural development and have also been identified as prognostic markers in malignancies of diverse origins. In the present study, we demonstrated that GNF‑5837, an inhibitor of TrkA and TrkB, suppressed the cell viability of renal carcinoma 786O and Caki‑2 cells in a concentration‑dependent manner. GNF‑5837 treatment led to decreased activities of TrkA and TrkB signaling, accompanied by reduced phosphorylation levels of AKT and extracellular signal‑regulated kinase (ERK) kinases, which was detected by western blot assay. GNF‑5837 induced G0/G1‑phase arrest and apoptosis. Consistently, GNF‑5837 affected the expression of p21, c‑Myc, and survivin proteins. Meanwhile, a wound healing assay showed that GNF‑5837 inhibited the migration ability of RCC cells by impairing Rac1 activity. GNF‑5837 also enhanced the cytotoxic effects of sunitinib via inhibition of ERK kinase. Taken together, these results identify the pharmacological potential of targeting Trk signaling as a therapeutic strategy for RCC.
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Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Wang H, Chen Y, Wang M, Ding G and Li T: Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma. Oncol Rep 42: 2039-2048, 2019.
APA
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., & Li, T. (2019). Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma. Oncology Reports, 42, 2039-2048. https://doi.org/10.3892/or.2019.7296
MLA
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., Li, T."Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma". Oncology Reports 42.5 (2019): 2039-2048.
Chicago
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., Li, T."Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma". Oncology Reports 42, no. 5 (2019): 2039-2048. https://doi.org/10.3892/or.2019.7296
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Wang H, Chen Y, Wang M, Ding G and Li T: Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma. Oncol Rep 42: 2039-2048, 2019.
APA
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., & Li, T. (2019). Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma. Oncology Reports, 42, 2039-2048. https://doi.org/10.3892/or.2019.7296
MLA
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., Li, T."Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma". Oncology Reports 42.5 (2019): 2039-2048.
Chicago
Chen, Y., Wang, H., Chen, Y., Wang, M., Ding, G., Li, T."Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma". Oncology Reports 42, no. 5 (2019): 2039-2048. https://doi.org/10.3892/or.2019.7296
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