MAPK抑制剂与组蛋白去乙酰化酶抑制剂对甲状腺癌细胞的联合再分化作用

发布时间：2018-04-26 06:42

本文选题：甲状腺癌 + 再分化治疗　；参考：《中国癌症杂志》2017年11期

【摘要】：背景与目的:应用MAPK抑制剂诱导再分化是治疗放射性碘难治性甲状腺癌的一种全新策略,但其临床有效率偏低。组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACI)是另一类诱导甲状腺癌再分化的药物,将其与MAPK抑制剂联合有可能提高再分化疗效。本研究旨在评估MAPK与HDACI联用是否能提高再分化的效果。方法:采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)、蛋白[质]印迹法(Western blot)、免疫荧光、流式细胞术、放射性核素摄取/流出及克隆形成等实验方法测试BRAF/MEK抑制剂(达拉非尼/司美替尼)及去乙酰化酶抑制剂(帕比司他)单药和联合用药时3种甲状腺癌细胞(BCPAP、K1和BHP 2-7)的碘和糖代谢相关基因的表达水平和功能状态。结果:达拉非尼/司美替尼可以一定程度提高BCPAP和K1细胞中碘代谢相关基因表达并抑制葡萄糖转运体表达;帕比司他对3种细胞都有一定的再分化作用。达拉非尼/司美替尼与帕比司他联合作用在BCPAP和K1细胞中取得较单药更好的再分化效果,在BHP 2-7中并未获得比单用帕比司他更明显的效果。结论:对具有BRAFV600E突变的甲状腺癌细胞应用达拉非尼/司美替尼和帕比司他联合用药,可以获得较单药更好的再分化效果。
[Abstract]:Background & AIM: redifferentiation induced by MAPK inhibitor is a new strategy for the treatment of radioactive iodine refractory thyroid carcinoma, but its clinical effective rate is low. Histone deacetylase inhibitor (HDACII) is another kind of drug that induces the redifferentiation of thyroid carcinoma. The combination of histone deacetylase inhibitor and MAPK inhibitor may improve the effect of redifferentiation. The purpose of this study was to evaluate whether the combination of MAPK and HDACI can improve the effect of redifferentiation. Methods: Real-time fluorescent quantitative polymerase chain reactionation (RTFQ-PCR), Western blottle, immunofluorescence and flow cytometry were used. Radionuclide uptake / efflux and clone formation were used to test BRAF/MEK inhibitor (dalafinil / sparmetinib) and deacetylase inhibitor (pabietam) alone and in combination with BCPAPAPK1 and BCPAPAPK1 in thyroid cancer cells. BHP 2-7) the expression level and functional status of genes related to iodine and glucose metabolism. Results: dalafinil / demetinib could increase the expression of iodine metabolism-related genes and inhibit the expression of glucose transporter in BCPAP and K1 cells to a certain extent, and pabestat had some redifferentiation effects on the three kinds of cells. The combination of dalafinil / demetinib and pabestatin had a better redifferentiation effect in BCPAP and K1 cells than that in BHP 2-7, but not in BHP 2-7. Conclusion: the combination of dalafinil / sparmetinib and pabestatin for thyroid cancer cells with BRAFV600E mutation can obtain better redifferentiation effect than that of single drug.
【作者单位】：上海交通大学附属第六人民医院核医学科;
【基金】：国家自然科学基金(81271609)
【分类号】：R736.1

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