阻断脉络丛中C3a受体活性对小鼠肺癌脑转移的影响

Effects of blocking C3a receptor activity in choroid plexus on brain metastasis of mice with lung cancer cells

目的:研究脉络丛中补体成分C3a对小鼠肺癌脑转移的促进作用及分子机制。方法:60只雄性BALB/c-nu/nu小鼠随机分为对照组、PC-14细胞注射组以及PC-14细胞联合SB290157处理组。利用尾静脉注射PC-14细胞方法制备BALB/c-nu/nu小鼠荷瘤模型,给予小鼠SB290157,通过商品化的试剂盒检测脑脊液中肿瘤细胞数量,ELISA检测脑脊液中C3a的水平,Western Blot方法检测脉络丛中C3a受体(C3aR)、紧密连接蛋白ZO-1和Claudin的表达。结果:通过尾静脉注射PC-14细胞方法制备成功制备脑转移瘤小鼠模型,SB290157处理显著降低小鼠脑转移灶的数量,荷瘤小鼠脉络丛中C3aR表达增加,ZO-1和Claudin的表达降低,脑脊液中C3a水平增加,SB290157处理后,ZO-1和Claudin的表达增加。结论:脉络丛中C3a及受体相互作用参与肺癌小鼠模型发生脑转移,其机制可能与破坏血脑屏障有关。

Objective: To study the promotion effect and molecular mechanism of complement component C3a in choroid plexus on brain metastasis of lung cancer in mice.Methods: sixty male BALB/C-nu/nu mice were randomly divided into control group,PC-14 cell injection group,and PC-14 cell combination SB290157 treatment group.The tumor-bearing model of BALB/C-nu/nu mice was prepared by injecting PC-14 cells into tail vein.SB 290157 was given to observe and detect the brain metastasis of tumor-bearing mice.Commercial kits were used to detect the number of tumor cells in CSF,The level of C3a in CSF was detected by ELISA,and the expressions of C3a receptor(C3aR),the tight junction protein ZO-1 and Claudin in choroid plexus were detected by Western Blot.Results: The mouse model of brain metastasis was successfully prepared by injecting PC-14 cells into tail vein.SB290157 treatment significantly reduced the number of brain metastasis in mice,increased the expression of C3aR in choroid plexus of tumor-bearing mice,decreased the expression of ZO-1 and Claudin,and increased the level of C3a in CSF.After SB290157 treatment,the expressions of ZO-1 and Claudin up-regulated.Conclusion: The interaction between C3a and receptor in choroid plexus is involved in brain metastasis in mice with lung cancer,and the mechanism may be related to the destruction of blood-brain barrier.