目的 研究去甲二氫愈創(chuàng)木酸（NDGA）類似物26C的抗肺癌活性與初步機制。方法 利用MTT實驗評價26C對肺癌細(xì)胞NCI-H460的細(xì)胞毒性；用集落克隆、劃痕實驗分別檢測26C對NCI-H460細(xì)胞生長、遷移的影響；流式細(xì)胞儀檢測26C對NCI-H460細(xì)胞的周期阻滯及誘導(dǎo)凋亡情況；活性氧簇（ROS）實驗探究26C引起細(xì)胞凋亡的作用機制。結(jié)果 26C對NCI-H460的IC₅₀為（4.7±0.5）μmol/L，對NCI-H460的集落形成、遷移有較強的抑制作用，其活性明顯優(yōu)于先導(dǎo)化合物NDGA；26C可將細(xì)胞周期阻滯在G₂/M期，并通過升高ROS水平的作用機制誘導(dǎo)NCI-H460細(xì)胞凋亡。結(jié)論 化合物26C為具有研發(fā)前景的抗肺癌候選化合物，其通過提高ROS水平、阻滯細(xì)胞周期來抑制細(xì)胞生長和誘導(dǎo)細(xì)胞凋亡。

Objective To study the anti-lung cancer activity and preliminary mechanism of NDGA analogue 26C. Methods MTT assay was employed to evaluate the cytotoxicity of 26C to lung cancer cells NCI-H460. Clonogenicity assay and scratch assay were used to investigate the role of 26C on proliferation and migration of NCI-H460 cells, respectively. Flow cytometry detected cycle arrest and apoptosis induction of NCI-H460 cells by 26C, and the intracellular accumulation of ROS was examined to explore the mechanism of 26C inducing apoptosis.Results 26C 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. 26C 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 26C could be considered as a potential anti-lung cancer candidate with promising prospects.

浙江省自然科學(xué)基金資助項目（LY15H280014）；云南大理藥業(yè)股份有限公司橫向課題（KJHX1603）