Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in non-thyroid cancer cells.

Abstract

BACKGROUND:

This study was designed to explore the therapeutic potential of suppressing MAP kinase and PI3K/Akt pathways and histone deacetylase (HDAC) to induce the expression of sodium/iodide symporter (NIS) and radioiodine uptake in non-thyroid cancer cells.

METHODS:

We tested the effects of the MEK inhibitor RDEA119, the Akt inhibitor perifosine, and the HDAC inhibitor SAHA on NIS expression in thirteen human cancer cell lines derived from melanoma, hepatic carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, and brain cancers. We also examined radioiodine uptake and histone acetylation at the NIS promoter in selected cells.

RESULTS:

Overall, the three inhibitors could induce NIS expression, to various extents, in melanoma and all the epithelial carcinoma-derived cells but not in brain cancer-derived cells. SAHA was most effective and its effect could be significantly enhanced by RDEA119 and perifosine. The expression of NIS, at both mRNA and protein levels, was most robust in the melanoma cell M14, hepatic carcinoma cell HepG2, and the gastric carcinoma cell MKN-7 cell. Radioiodine uptake was correspondingly induced, accompanied by robust increase in histone acetylation at the NIS promoter, in these cells when treated with the three inhibitors.

CONCLUSIONS:

This is the first demonstration that simultaneously suppressing the MAP kinase and PI3K/Akt pathways and HDAC could induce robust NIS expression and radioiodine uptake in certain non-thyroid human cancer cells, providing novel therapeutic implications for adjunct radioiodine treatment of these cancers.

• Authors: Zhi Liu, Mingzhao Xing
• Journal: PloS one (PLoS One) Vol. 7 Issue 2 Pg. e31729 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22359623 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Iodine Radioisotopes
• N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
• Sulfonamides
• Symporters
• Phosphorylcholine
• perifosine
• sodium-iodide symporter
• Vorinostat
• Diphenylamine
• Phosphatidylinositol 3-Kinases
• Mitogen-Activated Protein Kinase Kinases

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Cell Line, Tumor
• Diphenylamine (analogs & derivatives, pharmacokinetics)
• Histone Deacetylase Inhibitors
• Humans
• Hydroxamic Acids (pharmacology)
• Iodine Radioisotopes (pharmacokinetics)
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylcholine (analogs & derivatives, pharmacology)
• Signal Transduction (drug effects)
• Sulfonamides (pharmacokinetics)
• Symporters (genetics)
• Transcriptional Activation (drug effects)
• Vorinostat