本文選題：甲狀腺癌 + 再分化治療　； 參考：《中國癌癥雜志》2017年11期

【摘要】：背景與目的:應用MAPK抑制劑誘導再分化是治療放射性碘難治性甲狀腺癌的一種全新策略,但其臨床有效率偏低。組蛋白去乙�；敢种苿�(histone deacetylase inhibitor,HDACI)是另一類誘導甲狀腺癌再分化的藥物,將其與MAPK抑制劑聯(lián)合有可能提高再分化療效。本研究旨在評估MAPK與HDACI聯(lián)用是否能提高再分化的效果。方法:采用實時熒光定量聚合酶鏈反應(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)、蛋白[質]印跡法(Western blot)、免疫熒光、流式細胞術、放射性核素攝取/流出及克隆形成等實驗方法測試BRAF/MEK抑制劑(達拉非尼/司美替尼)及去乙�；敢种苿�(帕比司他)單藥和聯(lián)合用藥時3種甲狀腺癌細胞(BCPAP、K1和BHP 2-7)的碘和糖代謝相關基因的表達水平和功能狀態(tài)。結果:達拉非尼/司美替尼可以一定程度提高BCPAP和K1細胞中碘代謝相關基因表達并抑制葡萄糖轉運體表達;帕比司他對3種細胞都有一定的再分化作用。達拉非尼/司美替尼與帕比司他聯(lián)合作用在BCPAP和K1細胞中取得較單藥更好的再分化效果,在BHP 2-7中并未獲得比單用帕比司他更明顯的效果。結論:對具有BRAFV600E突變的甲狀腺癌細胞應用達拉非尼/司美替尼和帕比司他聯(lián)合用藥,可以獲得較單藥更好的再分化效果。
[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.
【作者單位】： 上海交通大學附屬第六人民醫(yī)院核醫(yī)學科;
【基金】：國家自然科學基金(81271609)
【分類號】：R736.1

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