Table 1.
NIS stimulators in thyroid cells in vitro.
| Agent | Mechanism of actiona | Cell lineb | NIS mRNA | NIS protein | I− uptakec | References |
|---|---|---|---|---|---|---|
| TSH | TSHR agonist | FRTL5 | up | up | 10~15 | (Kogai et al., 1997) |
| TSH | TSHR agonist | PCCL3 | up | ~30 | (Trapasso et al., 1999) | |
| TSH | TSHR agonist | Primary human thyroid | up | up | ~13 | (Kogai et al., 2000a; Saito et al., 1997) |
| Adenosine | ADRA1 agonist | FRTL5 | up | up | ~7.5 | (Harii et al., 1999) |
| TSH/LPSd | TLR4 agonist | FRTL5, PCCL3 | up | ~2.0 | (Nicola et al., 2009b) | |
| TSH/L-NAMEd | NOS inhibitor | FRTL5 | up | ~1.3 | (Fozzatti et al., 2007) | |
| TSH/KT5823d | cGK inhibitor | FRTL5 | ~2.2 | (Fozzatti et al., 2007) | ||
| TSH/LY294002d | PI3K inhibitor | FRTL5, PCCL3 | up | up | ~3.0 | (Kogai et al., 2008b) |
| TSH/Rapamycind | mTOR inhibitor | PCCL3 | up | ~2.5 | (de Souza et al., 2010) | |
| TSH/Resveratrold | Sirtuin activator | FRTL5 | up | ~3.0 | (Sebai et al., 2010) | |
| LY294002 | PI3K inhibitor | NIS-BHP2–7 (TPC1) | up | ~3.5 | (Kogai et al., 2008b) | |
| Akti-1/2 | AKT inhibitor | NIS-BHP2–7 (TPC1) | up | (Kogai et al., 2008b) | ||
| Depsipeptide | HDACi | FTC133, SW1736 | up | ~10 | (Kitazono et al., 2001) | |
| Trichostatin A | HDACi | BHP18–21v (TPC1) K1, FTC133, C643 |
up | up | ~3.0 | (Furuya et al., 2004) |
| SAHA | HDACi | KAT18, OCUT1 | up | (Hou et al., 2010) | ||
| SAHA/perifosinee | HDACi/AKTi | K1, C643 | up | (Hou et al., 2010) | ||
| SAHA/RDEA119e | HDACi/MEKi | K1, C643 | up | (Hou et al., 2010) | ||
| SAHA/RDEA119/perifosinef | HDACi/MEKi/AKTi | C643, FTC133 | up | (Hou et al., 2010) | ||
| SAHA/RDEA119/perifosine/TSH | HDACi/MEKi/AKTi/TSHR | K1, C643, KAT18 | up | 4~8 | (Hou et al., 2010) | |
| Sunitinib/forskolin | RTKi/AC agonist | TPC1 (BHP) | up | (Fenton et al., 2010) | ||
| Troglitazone | PPAR agonist | FTC133, TPC1 | up | (Park et al., 2005) | ||
| tRA | RAR agonist | FTC133 | up | (Schmutzler et al., 1997) | ||
| Lovastatin | HMGR inhibitor | CGTH | up | ~3 | (Frohlich et al., 2009) |
Abbreviations: ADRA1, adrenergic receptor α 1; NOS, nitric oxide synthase; cGK, cGMP-dependent protein kinase; mTOR, mammalian target of rapamycin; HMGR, HMG-CoA reductase; HDACi, HDAC inhibitor; AKTi, AKT inhibitor; MEKi, MEK inhibitor; RTKi, RTK inhibitor.
Origins of FRTL5 and PCCL3 are rat thyroid glands; BHP2–7, BHP18–21, K1, TPC1, papillary thyroid cancer; CGTH, FTC133, follicular thyroid cancer; C643, KAT18, OCUT1, undifferentiated (anaplastic) thyroid cancer.
Approximate fold-induction over the group without treatment is shown. Since specific activity of radioiodide in each study varies, values may not be compared among studies.
Enhances the TSH-induced NIS expression.
Enhances the SAHA-induced NIS expression.
Enhances the effects of double combination treatments.