分子化合物4-甲氧基苄基-N-甲基-4-苯乙烯酮-2-苯乙酰胺抑制肺癌细胞NCI-H1299转移的研究  

Inhibitory Effect of 4-Methoxybenzyl-N-Methyl-4-Phenylketene-2-Phenylacetamide on Metastasis of Lung Cancer Cells NCI-H1299

作　　者：陆俊鸿 邹青容 熊传伟 覃梅 吴甲媛 李映新[1] 曹思思 LU Jun-hong;ZOU Qing-rong;XIONG Chuan-wei;QIN Mei;WU Jia-yuan;LI Ying-xin;CAO Si-si(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《化学试剂》2024年第10期1-6,共6页Chemical Reagents

基　　金：国家自然科学基金项目(82060552);广西自然科学基金项目(2020GXNSFBA297057)。

摘　　要：探讨以转录因子叉头框C1(Forkhead box C1,FOXC1)蛋白结构为基础设计合成的标题化合物对肺癌细胞NCI-H1299的抑制作用。利用分子对接技术评估FOXC1与标题化合物的结合能力;MTT检测标题化合物对细胞增殖能力的影响;分别用5、10μmol/L标题化合物作用肺癌细胞NCI-H129912 h,Transwell实验检测标题化合物对细胞的迁移和侵袭能力的影响;构建稳定表达荧光素酶的肺癌细胞LUC-NCI-H1299,左心室注入小鼠体内构建转移瘤模型,分为对照组、低剂量(4 mg/kg)和高剂量(8 mg/kg)组,尾静脉注射治疗,观察化合物对肿瘤在体内转移的影响。结果表明FOXC1与标题化合物对接结合能为-6.9 kcal/mol,体外实验结果显示,化合物以剂量依赖方式抑制细胞增殖,其中低剂量和高剂量组对细胞的迁移和侵袭均有抑制效果,且高剂量组抑制效果更显著,体内研究发现,与对照组相比,标题化合物能有效抑制肺癌在体内的转移。综上,标题化合物与FOXC1能有效对接,在体外可抑制肺癌细胞的增殖、迁移和侵袭能力,在体内可减少肺癌细胞的转移。To investigate the inhibitory effect of 4-methoxybenzyl-N-methyl-4-phenylketene-2-phenylacetamide(A1)on lung cancer NCI-H1299,a compound was designed and synthesized based on the protein structure of the transcription factor Forkhead box C1(FOXC1).Molecular docking was used to evaluate the binding ability of FOXC1 to the A1.MTT was used to detect the effect of A1 on cell proliferation.Lung cancer cells NCI-H1299 were treated by A1 at the concentration of 5 and 10μmol/L for 12 h,respectively.Cell migration and invasion were evaluated using the transwell assay to determine the impact of A1.A stable lung cancer cell line(LUC-NCI-H1299)expressing luciferase was created and injected into the left ventricle to establish a metastatic tumor model in mice.The mice were divided into control,low-dose(4 mg/kg),and high-dose(8 mg/kg)groups.The effects of A1 on tumor metastasis in vivo were observed.The results indicated a binding energy of-6.9 kcal/mol between FOXC1 and A1.In vitro findings demonstrated a dose-dependent inhibition of cell proliferation by A1.Both low-dose and high-dose groups displayed inhibitory effects on cell migration and invasion,with the high-dose group showing a more pronounced effect.In vivo experiments revealed that A1 effectively suppressed lung cancer metastasis compared to the control group.In conclusion,the molecular compound A1 successfully bond to FOXC1,thereby inhibiting the proliferation,migration and invasion of lung cancer cells in vitro,and reducing the metastasis of lung cancer cells in vivo.

关 键 词：肺癌 4-甲氧基苄基-N-甲基-4-苯乙烯酮-2-苯乙酰胺 转移 FOXC1 分子对接 

分 类 号：R965[医药卫生—药理学]