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Li Y, Li Y, Liu Q, et al. Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells. Onco Targets Ther. 2015;8:1043-51doi: 10.2147/OTT.S70691.
Li, Y., Li, Y., Liu, Q., & Wang, A. (2015). Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells. OncoTargets and therapy, 81043-51. https://doi.org/10.2147/OTT.S70691
Li, Yanling, et al. "Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells." OncoTargets and therapy vol. 8 (2015): 1043-51. doi: https://doi.org/10.2147/OTT.S70691
Li Y, Li Y, Liu Q, Wang A. Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells. Onco Targets Ther. 2015 May 14;8:1043-51. doi: 10.2147/OTT.S70691. eCollection 2015. PMID: 25999739; PMCID: PMC4437616.
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Onco Targets Ther. 2015 May 14;8:1043-51. doi: 10.2147/OTT.S70691. eCollection 2015.

Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells.

OncoTargets and therapy

Yanling Li, Yuping Li, Qiang Liu, Aixue Wang

Affiliations

  1. Department of Dermatology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

PMID: 25999739 PMCID: PMC4437616 DOI: 10.2147/OTT.S70691

Abstract

Melanoma is the deadliest form of skin cancer, and BRAFV600E is a driver mutation that promotes melanoma growth and survival. PLX4032 is the first effective compound in clinical use for the treatment of patients with mutant BRAFV600. However, resistance to PLX4032 develops quickly within months. Activation of a series of receptor tyrosine kinases, including the platelet-derived growth factor receptor (PDGFR), has been identified to be the underlying mechanism for development of resistance to PLX4032. In this work, we investigated the anticancer activity of tyrphostin AG1296, a PDGFR inhibitor, in melanoma, especially PLX4032-resistant melanoma. We found that tyrphostin AG1296 could effectively reduce the viability of both PLX4032-sensitive and PLX4032-resistant melanoma cells. There is an additive effect between tyrphostin AG1296 and PLX4032 in reducing cell viability. Tyrphostin AG1296 induced dramatic apoptosis in PLX4032-resistant cells, and also dramatically inhibited migration of PLX4032-resistant cells. Importantly, tyrphostin AG1296 significantly suppressed A375R tumor growth in vivo. This is the first report on the anticancer activity of tyrphostin AG1296 in melanoma. Tyrphostin AG1296 is a promising compound in the treatment of melanoma, especially for those who have developed resistance towards BRAF inhibitors, and might shed new light on melanoma therapy.

Keywords: PLX4032; apoptosis; melanoma; migration; resistance; viability

References

  1. Nature. 2010 Dec 16;468(7326):968-72 - PubMed
  2. Nature. 2002 Jun 27;417(6892):949-54 - PubMed
  3. Nat Rev Cancer. 2002 Jul;2(7):489-501 - PubMed
  4. J Invest Dermatol. 2004 Feb;122(2):400-5 - PubMed
  5. N Engl J Med. 2010 Aug 26;363(9):809-19 - PubMed
  6. Cancer Res. 2013 Oct 15;73(20):6106-10 - PubMed
  7. Nature. 2012 Jul 26;487(7408):500-4 - PubMed
  8. Cancer Res. 2010 Aug 15;70(16):6670-81 - PubMed
  9. Trends Pharmacol Sci. 2013 Dec;34(12 ):656-66 - PubMed
  10. Nature. 2011 Oct 12;478(7369):349-55 - PubMed
  11. N Engl J Med. 2011 Jun 30;364(26):2507-16 - PubMed
  12. Wiley Interdiscip Rev Syst Biol Med. 2013 May-Jun;5(3):257-71 - PubMed
  13. Curr Opin Oncol. 2014 Mar;26(2):215-21 - PubMed
  14. J Biol Chem. 2012 Aug 10;287(33):28087-98 - PubMed
  15. J Clin Oncol. 2009 Dec 20;27(36):6199-206 - PubMed
  16. Nat Cell Biol. 2000 May;2(5):249-56 - PubMed
  17. J Clin Oncol. 2009 Jun 10;27(17):2823-30 - PubMed
  18. J Invest Dermatol. 2014 Feb;134(2):319-25 - PubMed
  19. Nature. 2007 Feb 22;445(7130):851-7 - PubMed
  20. Nature. 1994 Feb 3;367 (6462):474-6 - PubMed
  21. Cancer Cell. 2010 Dec 14;18(6):683-95 - PubMed
  22. Pharmacol Ther. 2013 Sep;139(3):405-11 - PubMed
  23. Nature. 2010 Dec 16;468(7326):973-7 - PubMed

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