安徽医学
安徽醫學
안휘의학
ANHUI MEDICAL JOURNAL
2014年
3期
269-271,272
,共4页
刘学谦%王新景%金佳斌%邓侠兴%沈柏用%彭承宏
劉學謙%王新景%金佳斌%鄧俠興%瀋柏用%彭承宏
류학겸%왕신경%금가빈%산협흥%침백용%팽승굉
胆管癌%融合基因%治疗靶点
膽管癌%融閤基因%治療靶點
담관암%융합기인%치료파점
Cholangiocarcinoma%Fusion gene%Therapeutic target
目的:寻找ROS激酶抑制剂,探索胆管细胞癌可能的新的治疗靶点。方法应用激酶抑制剂TAE684,评估其对融合基因及其下游效应的抑制作用。结果 TAE684对FIG-ROS(S)、FIG-ROS(L)呈剂量依赖性抑制,IC50分别为10 nM、1.8 nM,并能抑制其下游磷酸化作用。结论 FIG-ROS融合基因受某些抑制剂影响,有望成为治疗胆管癌的新靶点。胆管癌及其他肿瘤如肺癌、恶性胶质瘤中均发现ROS融合基因,临床研究需要更广泛地去筛查肿瘤中激活的ROS激酶。
目的:尋找ROS激酶抑製劑,探索膽管細胞癌可能的新的治療靶點。方法應用激酶抑製劑TAE684,評估其對融閤基因及其下遊效應的抑製作用。結果 TAE684對FIG-ROS(S)、FIG-ROS(L)呈劑量依賴性抑製,IC50分彆為10 nM、1.8 nM,併能抑製其下遊燐痠化作用。結論 FIG-ROS融閤基因受某些抑製劑影響,有望成為治療膽管癌的新靶點。膽管癌及其他腫瘤如肺癌、噁性膠質瘤中均髮現ROS融閤基因,臨床研究需要更廣汎地去篩查腫瘤中激活的ROS激酶。
목적:심조ROS격매억제제,탐색담관세포암가능적신적치료파점。방법응용격매억제제TAE684,평고기대융합기인급기하유효응적억제작용。결과 TAE684대FIG-ROS(S)、FIG-ROS(L)정제량의뢰성억제,IC50분별위10 nM、1.8 nM,병능억제기하유린산화작용。결론 FIG-ROS융합기인수모사억제제영향,유망성위치료담관암적신파점。담관암급기타종류여폐암、악성효질류중균발현ROS융합기인,림상연구수요경엄범지거사사종류중격활적ROS격매。
Objective To find the kinase inhibitor which works on the FIG-ROS and look for new potential therapeutic target for cholangiocarcinoma.Methods The kinase inhibitor TAE684 was used and its inhibiting ability on FIG-ROS kinase activity and downstream signaling molecules was evaluated.Results Kinase inhibitor TAE684 inhibited FIG-ROS(S),FIG-ROS(L)in a dose-dependent manner with IC50 10 nM,1.8 nMrespectively.Besides,it could also inhibit the crucial downstream signaling molecules of ROS kinase.Conclusion Our data demonstrates that FIG-ROS can be inhibited by kinase inhibitor,which may be a therapeutic target in cholangiocarcinoma.The iden-tification of ROS tyrosine kinase fusions in cholangiocarcinoma,lung cancer and glioblastoma,tells that a more broadly based screen for acti-vated ROS kinase in cancer is warranted.