June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Mitogen-activated protein kinase (MAPK) inhibitors in conjunctival melanoma cell lines
Author Affiliations & Notes
  • Jinfeng Cao
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Robert M. Verdijk
    Pathology, Erasmus Medical Center, Rotterdam, Netherlands
  • Aart G. Jochemsen
    Molecular Cell Biology, Leiden University Medical Center, Leiden, Netherlands
  • Martine J Jager
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Footnotes
    Commercial Relationships Jinfeng Cao, None; Robert Verdijk, None; Aart Jochemsen, None; Martine Jager, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1287. doi:
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      Jinfeng Cao, Robert M. Verdijk, Aart G. Jochemsen, Martine J Jager; Mitogen-activated protein kinase (MAPK) inhibitors in conjunctival melanoma cell lines. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1287.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Current therapies of conjunctival melanoma (CM) mainly focus on radical excision of the tumor, and are frequently supplemented with cryotherapy or local therapy. As activating mutations of BRAF and NRAS have been discovered in 47% of CMs, we studied the antitumor effect of mitogen-activated protein kinase (MAPK) inhibitors in CM cell lines.

Methods: Sanger sequencing was used to detect the mutation status of three human CM cell lines (CRMM1, CRMM2 and CM2005.1). The MEK inhibitor MEK162 (ARRY-162) and BRAF inhibitors Vemurafenib (PLX4032) and Dabrafenib (GSK2118436) were chosen to treat CM cells. Cell viability was determined with WST-1 and in-cell western assay. The phosphorylation status of ERK protein was evaluated using western blot.

Results: The BRAF T1799A mutation was identified in CRMM1 and CM2005.1, and the NRAS A182T mutation in CRMM2. The growth of all three CM cell lines was inhibited by MEK162 with a low concentration (IC50 < 45 nM). CRMM1 and CM2005.1 were sensitive to Vemurafenib (IC50 < 200 nM) and Dabrafenib (IC50 < 20 nM) in a dose-dependent manner, while CRMM2 was not. Consistent with the result of cell viability, a concentration-dependent decrease of ERK phosphorylation was detected in all three CM cell lines after MEK162 treatment, and in CRMM1 and CM2005.1 after Vemurafenib and Dabrafenib treatment. Paradoxically, the phosphorylated ERK of CRMM2 was activated by both BRAF inhibitors.

Conclusions: Growth inhibition of CM cell lines can be achieved by the appropriate MEK or BRAF inhibitors. Our findings demonstrate that MAPK inhibitors might be potential therapeutic drugs against conjunctival melanoma and its metastasis.


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