摘要
目的探索一种新的二代哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂9-(6-氨基-3-吡啶基)-1-[3-(三氟甲基)苯基]苯并[H]-1,6-萘啶-2(1H)-酮(Torin2)对人甲状腺乳头状癌(PTC)细胞生物学行为的影响,以期为临床靶向治疗PTC提供新的理论依据。方法对人PCT的TPC-1细胞株和正常甲状腺Nthy-ori-3细胞株运用不同浓度Torin2,分别采用四甲基偶氮唑盐(MTT)法检测细胞增殖能力,流式细胞仪分析细胞周期、凋亡情况,划痕愈合实验分析细胞迁移能力。结果 (1)与用药前相比,Nthy-ori-3细胞株均无明显变化;(2)各浓度(100、200、400 nmol/L)Torin2作用于TPC-1细胞24、48、72 h后,细胞增殖抑制率上升,差异有统计学意义(P<0.001),且随作用时间延长(24、48、72 h)和浓度增加,对细胞增殖抑制作用增强;(3)各浓度(100、200、400 nmol/L)Torin2作用于TPC-1细胞24、48 h后,G1期细胞比例逐渐增加,S期细胞比例逐渐下降,且具有时间和浓度依赖性,差异有统计学意义(P<0.001);(4)各浓度(100、200、400 nmol/L)Torin2作用于TPC-1细胞24、48 h后,细胞的凋亡率亦上升,呈现浓度依赖效应,差异有统计学意义(P<0.001);(5)各浓度(100、200、400 nmol/L)Torin2均可抑制TPC-1细胞的迁移,且随浓度的增加抑制能力越强,差异有统计学意义(P<0.001)。结论 Torin2可抑制TPC-1细胞的增殖及迁移、阻滞细胞周期、诱导细胞凋亡,并随着Torin2浓度的增加和作用时间延长而增强。
Objective To explore a new second-generation mammalian target of rapamycin(mTOR) inhibitor 9-(6-amino-3-pyridyl)-1-[3-(trifluoromethyl) phenyl] benzo[H]-1,6-naphthyridine-2(1 H)-one(Torin2) on the biological behavior of human papillary thyroid carcinoma(PTC) cells, so as to provide a new theoretical basis for clinical targeted treatment of PTC.Methods Human PTC cell line TPC-1 and human normal thyroid cell line Nthy-ori-3 were treated with different concentrations of Torin2. MTT colorimetry was used to detect cell proliferation, cell cycle and apoptosis were analyzed by flow cytometry, and cell migration was analyzed by scratching healing experiment.Results(1) Compared with that before administration, no significant change was observed in the human normal thyroid Nthy-ori-3 cell line;(2) different concentrations Torin2(100, 200, 400 nmol/L)after acting on TPC-1 cells 24, 48 and 72 h, cell proliferation inhibition rate gradually increased, and there was significant difference(P<0.001).And with the extension of action time(24,48,72 h) and the increase of concentration, the inhibition effect on cell proliferation was enhanced;(3)different concentrations Torin2(100, 200, 400 nmol/L)after acting on TPC-1 cells 24 and 48 h, the proportion of G1 phase cells gradually increased, while the proportion of S-phase cells gradually decreased, and there was significant difference(P<0.001), indicating significant time and concentration dependence;(4) different concentrations Torin2(100, 200, 400 nmol/L)after acting on TPC-1 cells 24 and 48 h, the apoptosis rate increased significantly and showed a concentration-dependent effect, and there was significant difference(P<0.001);(5) different concentrations Torin2(100, 200, 400 nmol/L)at each concentration could inhibit the migration of TPC-1 cells, and with the increase of the concentration, the inhibition ability was stronger, and there was significant difference(P<0.001).Conclusion Torin2 can significantly inhibit the proliferation and migration of human PTC TPC-1 cells, block cel
作者
孙洪莉
魏枫
梁书卿
王晓艳
郑朦
李冉浩
Sun Hongli;Wei Feng;Liang Shuqing(Dept of Endocrinology,the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014010)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第1期22-27,共6页
Acta Universitatis Medicinalis Anhui
基金
内蒙古自治区科技计划项目(编号:201802128)。
