常春藤皂苷元抑制胶质母细胞瘤细胞的增殖和迁移并诱导其凋亡OA北大核心CSTPCD
HDG inhibits the proliferation and migration of GBM cells and induces their apoptosis
目的 探讨常春藤皂苷元(HDG)对胶质母细胞瘤(GBM)细胞增殖、迁移和凋亡的影响及机制.方法 人GBM细胞株U87、U251和人脑胶质细胞株(HEB)为研究对象,以HDG 0μmol/L(或0 mg/kg)为对照组,实验组分别给予不同浓度HDG;噻唑蓝法(MTT)、EdU染色及细胞平板克隆检测HDG对GBM细胞增殖的影响;锥虫蓝染色检测HDG对GBM细胞死亡的影响;细胞划痕、Transwell实验检测HDG对GBM细胞迁移和侵袭的影响;Annexin V-FITC、JC-10染色及Western blot检测细胞凋亡相关蛋白B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2-Associated X的蛋白质Bax、肿瘤蛋白p53、胱天蛋白酶3(cleaved-caspase-3),分析HDG对GBM细胞凋亡的影响;BALB/C小鼠肿瘤异种移植实验分析HDG对GBM体内荷瘤的影响.结果 与对照组(HDG 0μmol/L)比较,HDG对U87、U251细胞的增殖、迁移和侵袭有显著抑制作用,且与HDG剂量呈依赖关系;锥虫蓝染色结果显示HDG导致GBM细胞的死亡数量明显增多;HDG明显诱导U87、U251细胞的线粒体膜电位下降、凋亡细胞数量增加以及凋亡相关蛋白Bax、p53、cleaved-caspase3的表达上调和Bcl-2的表达下调;HDG显著抑制BALB/C小鼠皮下GBM的大小、GBM细胞Ki67的阳性率并导致GBM细胞大量死亡;HDG对人HEB细胞以及荷瘤小鼠肝脏无明显毒性作用.结论 HDG对GBM细胞的增殖、迁移和侵袭有显著抑制作用且诱导其凋亡,HDG诱导GBM细胞凋亡的机制可能通过介导线粒体损伤及调控p53、Bcl-2/Bax表达.
Objective To investigate the effects of hederagenin (HDG) on proliferation, migration, invasion and apoptosis of glioblastoma (GBM) cells and involved mechanism.Methods Human GBM cell lines U87, U251 and human brain glial cell line (HEB) were selected as the study subjects, and HDG 0μmol/L (or 0 mg/kg) was used as the control group.MTT, EdU staining and cell plate cloning were used to detect the effect of HDG on the proliferation of GBM cells.Trypan blue staining was used to detect GBM cell death affected by HDG.The effects of HDG on migration and invasion of GBM cells were detected by cell scratch and Transwell assay.To analyze the effects of HDG on apoptosis of GBM cells, apoptosis-related proteins Bcl-2, Bax, p53 and cleaved caspase-3 were detected by Western blot.Mitochondrial potential change was detected by JC-10 staining, and apoptotic cell count was displayed by Annexin V-FITC staining.The effect of HDG on tumor bearing in GBM was analyzed by xeno-transplantation in BALB/C mice.Results Compared with the control group (HDG0 μmol/L), HDG significantly inhibited the proliferation, migration and invasion of U87 and U251 cells, and they were dependent on the use dose of HDG.Trypan blue staining showed that HDG obviously increased death number of GBM cells.The mitochondrial potential of GBM cells was remarkedly decreased, the number of apoptotic GBM cells obviously increased, the ex-pressions of apoptosis-related proteins p53, Bax, cleaved-caspase3 were up-regulated and Bcl-2 was down-regulated by HDG in U87 and U251 cells.HDG significantly inhibited the size of subcutaneous GBM, the Ki67 positive rate of GBM cells and caused a large number of GBM cells to die in BALB/C mice.HDG had no obvious toxic effect on human HEB cells and the liver of tumor-bearing mice.Conclusion HDG can significantly inhibit the prolifera-tion, migration and invasion of GBM cells and induce the apoptosis of them.The mechanism of HDG induced apop-tosis of GBM cells may be through mitochondrial damage and regulation of p53 and Bcl-2/Bax expression.
樊庆葵;余南琼;胡美纯;佘同辉
湖北科技学院医学部药学院,咸宁 437100||湖北科技学院医学部基础医学院,咸宁 437100湖北科技学院医学部基础医学院,咸宁 437100
临床医学
常春藤皂苷元胶质母细胞瘤增殖迁移凋亡
hederageninglioblastomaproliferationmigrationapoptosis
《安徽医科大学学报》 2024 (005)
852-863 / 12
湖北省自然科学基金(编号:2022CFB394);湖北省科技计划项目(编号:2016CFB491);湖北省卫生健康委员会科研项目(编号:WJ2019Q022);湖北科技学院医学科研专项基金(编号:2022YKY07、2022YKY08)
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