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小分子化合物O-565抑制胃癌细胞迁移侵袭及机制研究
引用本文:王希明,张晔,刘云鹏,穆晓东,曲秀娟,侯科佐,康健,胡雪君. 小分子化合物O-565抑制胃癌细胞迁移侵袭及机制研究[J]. 现代肿瘤医学, 2014, 0(5): 1024-1027
作者姓名:王希明  张晔  刘云鹏  穆晓东  曲秀娟  侯科佐  康健  胡雪君
作者单位:[1]中国医科大学第一附属医院呼吸内科,辽宁沈阳110001 [2]中国医科大学第一附属医院肿瘤内科,辽宁沈阳110001
基金项目:国家自然科学基金项目(编号:81270036);辽宁省自然科学基金项目(编号:2013021057,2011404013-5)
摘    要:目的:研究小分子化合物O-565对人胃癌细胞BGC823、MKN-45增殖、迁移和侵袭能力的影响及其作用机制。方法:应用MTT检测不同浓度小分子化合物O-565对胃癌细胞BGC823和MKN-45增殖能力的影响。分别用0、20、40、60μmol/L浓度的化合物O-565处理BGC823和MKN-45两种胃癌细胞,应用Transwell小室检测其对上述两种细胞迁移侵袭能力的抑制作用,Westernblot检测化合物对金属基质蛋白酶2(MMP-2)表达及丝切蛋白(Cofilin)磷酸化水平的影响。结果:化合物O-565对于BGC823和MKN-45两种胃癌细胞的增殖能力无明显影响,却能够以剂量依赖的方式抑制上述细胞的迁移和侵袭。Westernblot结果显示O-565能够下调胃癌细胞BGC823中MMP-2的表达及Cofilin的磷酸化水平。结论:化合物O-565可能通过下调细胞中MMP-2的表达及Cofilin的磷酸化水平,抑制BGC823、MKN-45胃癌细胞的迁移和侵袭。

关 键 词:O-565  胃癌  侵袭  MMP-2  Cofilin

Icotinib inhibits proliferation and induces apoptosis via inactivation of the c - Cbl depend-ent MAPK/ERK pathway in human HCC827 lung cancer cells
Wang Ximing,Zhang Ye,Liu YunPeng,Mu Xiaodong,Qu Xiujuan,Hou Kezuo,Kang Jian,Hu Xuejun. Icotinib inhibits proliferation and induces apoptosis via inactivation of the c - Cbl depend-ent MAPK/ERK pathway in human HCC827 lung cancer cells[J]. Journal of Modern Oncology, 2014, 0(5): 1024-1027
Authors:Wang Ximing  Zhang Ye  Liu YunPeng  Mu Xiaodong  Qu Xiujuan  Hou Kezuo  Kang Jian  Hu Xuejun
Affiliation:1 Department of Respiratory Disease, the First Hospital, China Medical University, Liaoning Shenyang 110001, China; 2 Department of Medical Oncology,the First Hospital, China Medical University,Liaoning Shenyang 110001 ,China)
Abstract:Objective:To investigate the role of c - Cbl involved in inactivation of MAPK/ ERK Pathway induced by Icotinib. Methods:The effect of Icotinib on the Proliferation of eCC827 was detected by MTT. Cell aPoPtosis was determined by flow cytometry with Annexin V - PI staining. Protein exPression levels were detected by Western blot. All exPerimental data was analyzed with SPSS 18. 0 software. Results:The IC50 value of eCC827 incuabted with Ico-tinib for 24h was 155. 6 μmol/ L;Icotinib induced the aPoPtosis of eCC827 in a dose - dePendent manner. Western blot results showed that Icotinib decreased the exPression level of P - EGFR,P - ERK and c - Cbl. Conclusion:Ico-tinib significantly inhibits eCC827 Proliferation by inducing aPoPtosis. The reason is that c - Cbl leads to inactivation of MAPK/ ERK Pathway as showed by downregualtion of P - EGFR and P - ERK.
Keywords:Icotinib  NSCLC  MAPK/ ERK Pathway  c-Cbl
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