Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in non-thyroid cancer cells.
Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in non-thyroid cancer cells.
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DOI：
10.1371/journal.pone.0031729
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xing M
中科院分区：
文献类型：
--
作者：
Liu Z;Xing M
本研究旨在探索抑制 MAP 激酶和 PI3K/Akt 通路以及组蛋白脱乙酰酶 (HDAC) 诱导非甲状腺癌细胞中钠/碘同向转运体 (NIS) 表达和放射性碘摄取的治疗潜力。我们测试了 MEK 抑制剂 RDEA119、Akt 抑制剂哌立福辛和 HDAC 抑制剂 SAHA 对来自黑色素瘤、肝癌、胃癌、结肠癌、乳腺癌和脑癌的 13 种人类癌细胞系中 NIS 表达的影响。我们还检查了选定细胞中 NIS 启动子的放射性碘摄取和组蛋白乙酰化。总体而言，这三种抑制剂可以不同程度地在黑色素瘤和所有上皮癌衍生细胞中诱导 NIS 表达，但不能在脑癌衍生细胞中诱导 NIS 表达。 SAHA 最为有效，RDEA119 和哌立福辛可显着增强其效果。 NIS 在 mRNA 和蛋白质水平上的表达在黑色素瘤细胞 M14、肝癌细胞 HepG2 和胃癌细胞 MKN-7 中最强。当用三种抑制剂处理时，这些细胞中的放射性碘摄取相应地被诱导，同时 NIS 启动子处的组蛋白乙酰化显着增加。这是首次证明同时抑制 MAP 激酶和 PI3K/Akt 通路以及 HDAC 可以在某些非甲状腺人类癌细胞中诱导强大的 NIS 表达和放射性碘摄取，为这些癌症的辅助放射性碘治疗提供新的治疗意义。
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. 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. 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. 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.
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影响因子：
10.6
作者：
MCDOUGALL, IR
通讯作者：
MCDOUGALL, IR
DOI：
10.1158/1078-0432.ccr-10-1627
发表时间：
2010-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu Z;Liu D;Bojdani E;El-Naggar AK;Vasko V;Xing M
通讯作者：
Xing M
影响因子：
3.7
作者：
Hou P;Liu D;Ji M;Liu Z;Engles JM;Wahl RL;Xing M
通讯作者：
Xing M
DOI：
10.1097/01.iop.0000179369.75569.a8
发表时间：
2005-09-01
影响因子：
2
作者：
Morgenstern, Kenneth E.;Vadysirisack, Douangsone D.;Jhiang, Sissy M.
通讯作者：
Jhiang, Sissy M.
影响因子：
5.8
作者：
Arturi, F;Russo, D;Filetti, S
通讯作者：
Filetti, S