摘要目的 探讨曲古菌素A(TSA)对甲状腺癌细胞中钠/碘同向转运蛋白(NTIS)基因表达和摄取碘的影响.方法 以不同浓度的TSA诱导滤泡状甲状腺癌细胞FTC-133及乳头状甲状腺癌细胞KI,利用反转录-聚合酶链反应(RT-PCR)分析经诱导后2株甲状腺癌细胞中NIS mRNA的表达,以NIS/3-磷酸甘油醛脱氧酶(GAPDH)的条带密度比值作为mRNA表达强度,并检测诱导前后甲状腺癌细胞对放射性碘摄取的变化.2组数据间比较采用独立样本t检验,多组数据间比较用One-wayANONA方差分析.结果 20,50,75,100和150 nmol/L TSA诱导48 h后.甲状腺癌细胞FTC-133的NIS mRNA表达较未诱导对照组增加了1.5至13.7倍,各TSA浓度组间FTC-133 NIS mRNA表达差异有统计学意义(F=32.56,P<0.01);而K1的NIS mRNA表达没有明显变化,TSA浓度为50和75 nmol/L时表达有所增加(NIS/GAPDH条带密度比值分别为0.62±0.16,0.60±0.23),但与对照组(0.41±0.18)比较差异无统计学意义(F=2.823,P>0.05).细胞摄取碘实验显示,50和75 nmol/L TSA诱导48 h后,FTC-133的摄碘增加[(15.42±0.42)×10~3和(18.98±1.33)×10~3计数·min~(-1)/10~5个细胞],与对照组[(8.46±0.84)×10~3计数·min~(-1)/10~5个细胞]比较,差异有统计学意义(t值分别为3.018和3.557,P均<0.05);而50和75 nmol/L TSA作用后K1对碘的摄取也有增加[(5.83±1.09)×10~3和(6.97±0.65)×10~3计数·min~(-1)/10~5个细胞],但与对照组[(5.37±0.88)×10~3计数·min~(-1)/10~5个细胞]比较,差异无统计学意义(t值分别为0.185和0.332,P均>0.05).结论 TSA能明显诱导滤泡状甲状腺癌细胞的NIS mRNA表达升高和摄碘增加,而对乳头状甲状腺癌细胞作用不明显.

abstractsObjective To investigate the sodium/iodide symporter (NIS) expression and iodide uptake in thyroid cancer cells induced by the histone deacetyltransferase inhibitors (HDACi), Trichostatin A (TSA). Methods Both the thyroid cancer cell lines, follicular thyroid carcinoma cell line FTC-133 and papillary thyroid carcinoma cell line K1, were firstly induced with TSA for 48 h. Then, the expression of NIS mRNA was analysed with reverse transcription-polymerase chain reaction (RT-PCR), the densitometric ratio of NIS/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was calculated, and the iodide uptake in the thyroid cancer cells was also measured. Independent-sample t-test and one-way analysis of variance (ANOVA) were used to analyze the data. Results For FTC-133 cells, increased NIS mRNA expression was detected after 48 h of TSA treatment, and the changes were dose-dependent (F=32.56, P<0.01).No obvious increasing expression of NIS mRNA was observed in K1 cells after 48 h of TSA treatment (F=2.823, P >0.05). Furthermore, FTC-133 cells showed the ability of accumulating radioiodide with 50 and 75 nmol/L TSA induction for 48 h: (15.42±0.42)×10~3 counts·min~(-1)·10~(-5) cells vs (8.46±0.84)× 10~3 counts·min~(-1)·10~(-5) cells, t=3.018, P<0.05; (18.98±1.33)×10~3 counts·min~(-1)·10~(-5) cells vs (8.46±0.84)×10~3 counts·min~(-1)·10~(-5) cells, t=3.557, P<0.05, respectively, while radioiodide uptake in K1 displayed no significant change after TSA induction: (5.83±1.09)×10~3 counts·min~(-1)·10~(-5) cells, (6.97±0.65)×10~3 counts·min~(-1)·10~(-5) cells vs (5.37±0.88)×10~3 counts·min~(-1)·10~(-5) cells, t=0.185, P> 0.05 and t = 0.332, P > 0.05, respectively. Conclusion TSA induced upregulated NIS mRNA expression in follicular thyroid cancer cells and augmented radioiodide uptake in thyroid cancer cells, while TSA had no remarkable effect on papillary thyroid carcinoma cell.