Drp1在低氧诱导胶质母细胞瘤U251细胞迁移中的作用

发布时间：2018-08-29 09:28

【摘要】：胶质母细胞瘤是最常见的脑肿瘤，具有极强的迁移和浸润能力，其发病率和致死率都很高。临床上胶质母细胞瘤无论良性和恶性均呈浸润性生长，边界不清楚，是常见的实体瘤。众所周知实体瘤共有的特性是其中央区域处于低氧的微环境。研究表明，低氧诱导因子HIF-1α是肿瘤细胞激活迁移的基本启动因子，，在胶质母细胞瘤细胞中同样证实了这一点。目前，有研究表明线粒体动态参与肿瘤细胞的迁移和浸润，然而低氧条件下Drp1参与人类胶质母细胞瘤细胞迁移和浸润的确切机制尚不明了。目前的研究表明低氧条件下Drp1的转录和表达上调，激活U251细胞中线粒体的分裂。利用HIF-1α的抑制剂棘霉素抑制HIF-1α，能够阻断低氧诱导的Drp1的表达。利用Drp1的抑制剂Mdivi-1能够有效的削弱低氧条件下线粒体的分裂和U251细胞的迁移。为了进一步的验证Drp1参与的胶质母细胞瘤细胞U251的迁移，我们建立了三个稳定表达的细胞系：GFP，GFP-Drp1和Drp1显性突变失活的GFP-Drp1-K38A。MTT实验表明三种稳定表达细胞系迁移速度没有明显的差异。低氧条件下表达显性失活的GFP-Drp1-K38A的细胞系和表达GFP的稳定细胞系相比，GFP-Drp1-K38A的细胞系能够减弱低氧诱导的胶质母细胞瘤细胞的迁移；然而稳定表GFP-Drp1的细胞系能够加快低氧条件下U251细胞的迁移。因此，我们的研究表明： Drp1参与低氧诱导的胶质母细胞瘤细胞U251的迁移。Drp1在未来有可能成为抑制胶质母细胞瘤细胞迁移的一个潜在靶点。
[Abstract]:Glioblastoma is the most common brain tumor, with strong migration and infiltration ability, its morbidity and mortality are very high. Glioblastoma is a common solid tumor. It is well known that the common feature of solid tumors is that their central region is in a low-oxygen microenvironment. The results show that hypoxia inducible factor HIF-1 伪 is the basic promoter of tumor cell activation and migration, which is also confirmed in glioblastoma cells. At present, some studies have shown that mitochondria dynamically participate in the migration and infiltration of tumor cells. However, the exact mechanism of Drp1 involved in the migration and infiltration of human glioblastoma cells under hypoxic conditions is not clear. Current studies have shown that Drp1 transcription and expression are up-regulated and activated mitochondrial division in U251 cells under hypoxia. Echinomycin, an inhibitor of HIF-1 伪, inhibited the expression of HIF-1 伪 and blocked the expression of Drp1 induced by hypoxia. Mdivi-1, an inhibitor of Drp1, can effectively weaken mitochondrial division and U251 cell migration under hypoxia. To further verify the role of Drp1 in the migration of glioblastoma cell line U251, we established three stable expression cell lines: GFP GFP-Drp1 and GFP-Drp1-K38A.MTT with Drp1 dominant mutation inactivation. The results showed that there was no significant difference in migration speed between the three stable expression cell lines. The cell lines expressing dominant inactivated GFP-Drp1-K38A and stable cell lines expressing GFP could attenuate the migration of glioblastoma cells induced by hypoxia compared with those of GFP-Drp1-K38A cells. However, stable epidermal GFP-Drp1 cell lines can accelerate the migration of U251 cells under hypoxia. Therefore, our study suggests that Drp1 may be a potential target for inhibiting glioblastoma cell migration in the future.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41

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