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

  • Published online on: August 28, 2019     https://doi.org/10.3892/or.2019.7296
  • Pages: 2039-2048
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

November-2019
Volume 42 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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