title: In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma.
abstract: Anaplastic thyroid carcinoma (ATC) is a severe thyroid malignancy with poor prognosis, due to its early metastasis and unresponsiveness to both radiation and chemotherapy. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, has been used as a re-differentiation agent to treat cancers in several human cancer models. So far, the effects of nevirapine on human thyroid anaplastic carcinoma cells have not been documented. The aim of this study was to evaluate the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Cell proliferation was determined by methly thiazolyl tetrazolium (MTT) assay. Cell apoptosis was analyzed by Hoechst 33258 staining. The mRNA expression of NIS and TSHR was determined by real-time quantitative reverse transcription-polymerase chain reaction (real time RT-PCR). Iodine uptake was determined by (125)I radioactivity assay. At all doses (100, 200, 350, 500 μmol/L) tested, nevirapine significantly inhibited cell proliferation after 48 h treatment. At high dose (500 μmol/L), nevirapine significantly increased the percentage of apoptotic cells compared with control (P<0.01). At lower doses (200 μmol/L and 350 μmol/L), nevirapine did not induce cell apoptosis, but up-regulated NIS and THSR mRNA expression in a dose-dependent manner. In FRO cells pre-treated with nevirapine, the increase in NIS expression had no obvious effect on iodine uptake. These findings indicate that nevirapine has an anti-proliferative effect on FRO cells, which correlates with an induction of cell differentiation.
authors: Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
authors: J J
authors: JJ
authors: Dong
authors: Y
authors: Y
authors: Zhou
authors: Y T
authors: YT
authors: Liu
authors: Z W
authors: ZW
authors: Zhang
authors: X J
authors: XJ
authors: Zhou
authors: H J
authors: HJ
authors: Wang
authors: L
authors: L
authors: Liao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D019829:Nevirapine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011989:Receptors, Thyrotropin / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D027981:Symporters / Q000235:genetics; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D000099209:Sodium-Iodide Symporters
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019829:Nevirapine; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D018894:Reverse Transcriptase Inhibitors; D027981:Symporters; D000099209:Sodium-Iodide Symporters