摘要
目的 研究去甲二氢愈创木酸(NDGA)类似物26C的抗肺癌活性与初步机制.方法 利用MTT实验评价26C对肺癌细胞NCI-H460的细胞毒性;用集落克隆、划痕实验分别检测26C对NCI-H460细胞生长、迁移的影响;流式细胞仪检测26C对NCI-H460细胞的周期阻滞及诱导凋亡情况;活性氧簇(ROS)实验探究26C引起细胞凋亡的作用机制.结果 26C对NCI-H460的IC50为(4.7±0.5)μmol/L,对NCI-H460的集落形成、迁移有较强的抑制作用,其活性明显优于先导化合物NDGA;26C可将细胞周期阻滞在G2/M期,并通过升高ROS水平的作用机制诱导NCI-H460细胞凋亡.结论 化合物26C为具有研发前景的抗肺癌候选化合物,其通过提高ROS水平、阻滞细胞周期来抑制细胞生长和诱导细胞凋亡.
Objective To study the anti-lung cancer activity and preliminary mechanism of NDGA analogue 26 C.Methods MTT assay was employed to evaluate the cytotoxicity of 26 C to lung cancer cells NCI-H460.Clonogenicity assay and scratch assay were used to investigate the role of 26 C on proliferation and migration of NCI-H460 cells,respectively.Flow cytometry detected cycle arrest and apoptosis induction of NCI-H460 cells by 26 C,and the intracellular accumulation of ROS was examined to explore the mechanism of 26 C inducing apoptosis.Results 26 C own an IC50 value of(4.7±0.5) μmol/L,and displayed a potent inhibition on clonogenicity and migration in NCI-H460 cells.Additionally,its activity was obviously better than the leading compound NDGA.26 C could arrest the cell cycle in the G2/M phase and induce apoptosis by accumulating the intracellular ROS.Conclusion With activities of inhibit cell growth and induce apoptosis by increasing ROS levels and arresting the cell cycle,compound 26 C could be considered as a potential anti-lung cancer candidate with promising prospects.
作者
李倩
赵祺
秦宇雯
吴建章
吴晓萍
姜程曦
LI Qian;ZHAO Qi;QIN Yuwen;WU Jianzhang;WU Xiaoping;JIANG Chengxi(Department of Pharmacy,Wenzhou Medical University,Wenzhou 325035,China;Institute of Life Sciences,Wenzhou University,Wenzhou 325035,China;Institute of Tissue Transplantation and Immunology,Jinan University,Guangzhou 510632,China)
出处
《药物评价研究》
CAS
2019年第11期2153-2158,共6页
Drug Evaluation Research
基金
浙江省自然科学基金资助项目(LY15H280014)
云南大理药业股份有限公司横向课题(KJHX1603)
