The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors

Sci Rep. 2019 Mar 13;9(1):4390. doi: 10.1038/s41598-019-40818-w.


CXCL8 is a chemokine secreted by normal and thyroid cancer cells with proven tumor-promoting effects. The presence of BRAFV600E mutation is associated with a more aggressive clinical behavior and increased ability to secrete CXCL8 by papillary-thyroid-cancer cells. Aim of this study was to test the effect of the BRAF-inhibitor (PLX4720) on the basal and TNF-α-induced CXCL8 secretions in BRAFV600E mutated (BCPAP, 8305C, 8505C), in RET/PTC rearranged (TPC-1) thyroid-cancer-cell-lines and in normal-human-thyrocytes (NHT). Cells were incubated with increasing concentrations of PLX4720 alone or in combination with TNF-α for 24-hours. CXCL8 concentrations were measured in the cell supernatants. PLX4720 dose-dependently inhibited the basal and the TNF-α-induced CXCL8 secretions in BCPAP (F: 14.3, p < 0.0001 for basal and F: 12.29 p < 0.0001 for TNF-α), 8305C (F: 407.9 p < 0.0001 for basal and F: 5.76 p < 0.0001 for TNF-α) and 8505C (F:55.24 p < 0.0001 for basal and F: 42.85 p < 0.0001 for TNF-α). No effect was found in TPC-1 (F: 1.8, p = 0.134 for basal; F: 1.6, p = 0.178 for TNF-α). In NHT an inhibitory effect was found only at the highest concentration of PLX4720 (F: 13.13 p < 0.001 for basal and F: 2.5 p < 0.01 for TNF-α). Cell migration assays showed that PLX4720 reduced both basal and CXCL8-induced cell migration in BCPAP, 8305C, 8505C and NHT but not in TPC-1 cells. These results constitutes the first demonstration that PLX4720 is able to inhibit the secretion of CXCL8 in BRAFV600E mutated thyroid cancer cells indicating that, at least some, of the anti-tumor activities of PLX4720 could be exerted through a lowering of CXCL8 in the thyroid-cancer-microenvironment.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cells, Cultured
  • Humans
  • Indoles / pharmacology*
  • Interleukin-8 / metabolism*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sulfonamides / pharmacology*
  • Thyroid Epithelial Cells / drug effects*
  • Thyroid Epithelial Cells / metabolism*
  • Thyroid Neoplasms / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Wound Healing / drug effects


  • CXCL8 protein, human
  • Indoles
  • Interleukin-8
  • PLX 4720
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins B-raf