摘要
目的探讨雷帕霉素靶蛋白(mTOR)抑制剂依维莫司与全反式维甲酸(ATRA)联用对小细胞肺癌细胞株NCI-H446增殖及迁移能力的影响。方法将不同浓度ATRA分别和依维莫司联合作用于NCI-H446细胞,采用MTT试验检测药物作用24h、48h、72h后的细胞存活率;细胞划痕实验观测药物处理24h后的细胞迁移能力。不同药物浓度作用于荷瘤小鼠,通过裸鼠移植瘤模型观察全反式维甲酸与依维莫司的体内协同抑瘤作用。结果MTT实验表明ATRA联合依维莫司抑制NCI-H446细胞增殖呈时间及浓度依赖性,高浓度联合用药组72h细胞存活率最低;划痕实验结果表明联合用药组抑制细胞迁移作用显著,ARTA药物浓度越高迁移抑制作用越强;裸鼠皮下抑制瘤模型中各组在给药3周后发现联合用药组抑瘤作用高于依维莫司组和对照组。结论依维莫司与ATRA联合应用在抑制人小细胞肺癌细胞增殖、迁移方面具有协同作用,在小细胞肺癌治疗可能具有良好的临床应用前景。
Objective The purpose of this study is to investigate the effects of rapamycin target protein(mTOR)inhibitor everolimus alone or everolimus combined with all-trans retinoic acid(ATRA)on proliferation and migration of small cell lung cancer cell line NCI-H446.Methods NCI-H446 cells were treated with different concentrations of ATRA combining with everolimus.MTT assay was used to detect the cell viability after 24,48 and 72 hours.Would healing assays was used to observe the cell migration ability after 24 hours of drug treatment.Xenograft model was created by implanting H446 cells subcutaneously,then treated with different concentrations of ATRA and everolimus.The tumor volumes were measured every 3 days.Results MTT assays showed that ATRA had a concentration and time-dependent effect on the small cell lung cancer cell line NCI-H446.High concentration of ATRA combined with everolimus could inhibit the proliferation of NCI-H446 cells obviously.Would healing assays showed that high concentration of ATRA could significantly inhibit NCI-H446 cell migration.The higher the concentration of ARTA,the stronger the inhibition on cell migration.In the 3rd week the tumor size of nude mice in the experiment group was smaller than the control group,The growth of tumor in the experiment group was slower than that in the control group which had a statistical significance.Conclusion ATRA combined with the mTOR inhibitor everolimus can sensitize the NCI-H446 cells to everolimus,which may have a good clinical application prospect in the treatment of small cell lung cancer.
出处
《江西医药》
CAS
2021年第2期136-138,153,共4页
Jiangxi Medical Journal
基金
江西省卫生计生委科技计划,编号20187274。
关键词
依维莫司
全反式维甲酸
小细胞肺癌
Everolimus
All-trans Retinoic Acid
Small Cell Lung Cancer
