百合总皂苷对肺癌细胞增殖、凋亡及侵袭转移的作用及其初步机制研究  

Study on effects of total saponins from Lilii Bulbus on proliferation,apoptosis,invasion and metastasis of lung cancer cells and its preliminary mechanism

作　　者：罗林明[1,2] 覃丽 詹济华[1] 裴刚 周小江[1,2] 陈乃宏 LUO Lin-ming;QIN Li;ZHAN Ji-hua;PEI Gang;ZHOU Xiao-jiang;CHEN Nai-hong(College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Engineering Technology Research Center of Standardization and Function of Traditional Chinese Medicine Decoction Pieces in Hunan Province,Changsha 410208,China;Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Belling 100050,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]湖南省中药饮片标准化及功能工程技术研究中心,湖南长沙410208 [3]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中国中药杂志》2018年第22期4498-4505,共8页China Journal of Chinese Materia Medica

基　　金：国家发改委国家中医药管理局项目(ZYBZH-Y-HUN-24,ZYBZH-Y-HEB-16);湖南省中药饮片标准化及功能工程技术研究中心开放课题(BG201706);湖南省科技创新平台建设项目(2016TP2008)

摘　　要：该文探讨百合总皂苷(TSLL)对人肺癌A549细胞增殖、凋亡、迁移及侵袭的潜在作用及其可能机制。采用CCK-8法、克隆形成实验及Ed U染色检测TSLL对A549细胞增殖的影响,Annexin V/PI双染法和Hoechst 33342染色法荧光显微镜观察TSLL对细胞凋亡形态的影响,Transwell迁移实验和Transwell侵袭实验分别检测TSLL对细胞迁移、侵袭的影响,Western blot法检测TSLL对肿瘤细胞内相关蛋白的表达变化。结果显示,TSLL干预肺癌A549细胞24,48或72 h均可显著抑制细胞生长,其IC50分别约为229,173,71 mg·L-1;TSLL可显著降低A549细胞克隆形成率;TSLL可浓度依赖性地降低A549细胞DNA合成率;TSLL可明显诱导A549细胞凋亡;TSLL可减少A549细胞迁移行为;TSLL可减少A549细胞侵袭人工基底膜;TSLL可显著下调肺癌A549细胞内PCNA蛋白的表达水平以及Bcl-2/Bax蛋白表达水平比值,同时促进procaspase 3的激活,此外TSLL对EMT相关标志蛋白E-cadherin,vimentin的表达均无明显的影响。以上结果表明TSLL对肺癌A549细胞增殖、迁移及侵袭具有抑制作用,并且对细胞凋亡具有诱导作用。TSLL可通过下调PCNA的表达抑制肺癌细胞DNA合成,从而抑制细胞增殖。TSLL对肺癌细胞凋亡的诱导作用与其对Bcl-2,Bax蛋白的表达调控有关。此外,TSLL抗肺癌细胞侵袭转移作用与EMT无明显的关联性。The potential role of total saponins extracted from Lilium lancifolium bulbs(TSLL) on the proliferation,apoptosis,migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8,clone formation assay and Ed U staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test,respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24,48 or 72 h significantly inhibited cell growth,and its IC50 values were about 229,173 and 71 mg·L-1,respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner.TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition,TSLL had no obvious effect on epithelial mesenchymal transition(EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation,migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless,there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer ce

关 键 词：百合 总皂苷 肺癌 增殖 凋亡 侵袭转移 机制 

分 类 号：R285[医药卫生—中药学]