Lumican基因过表达对肺腺癌细胞A549转移的影响及机制探讨

Effect and Mechanism of Lumican Gene Overexpression on Metastasis of Lung Adenocarcinoma Cell A549

基膜聚糖(Lumican)广泛分布于人体各组织,并在多种恶性肿瘤组织中异常表达,在肿瘤的迁移、黏附和转移灶的形成等过程中起重要作用。该研究首先构建稳定过表达Lumican基因的细胞株,采用Transwell小室、黏附、血管形成及动物实验检测各组细胞侵袭、迁移,同、异种细胞间黏附及血管形成能力,研究其对肺腺癌细胞A549转移能力的影响;并通过Western blot检测RhoC、p-Akt、MMP-2、VEGF蛋白的表达,探讨其可能机制。结果发现,与空载体组和(或)对照组比较,实验组细胞侵袭、迁移能力增强(P<0.05),同种细胞间黏附力减弱(P<0.05)、异种细胞间粘附力增强(P<0.05),血管形成能力及裸鼠皮下瘤血管密度增加(P<0.05),RhoC、p-Akt、MMP-2、VEGF蛋白表达均明显增加(P<0.05),以上各参数比较对照组与空载体组之间均没有明显差异(P>0.05)。该研究表明,Lumican基因在肺腺癌细胞A549中过表达能促进细胞的转移,其机理可能与RhoC蛋白表达增高有关。

Lumican which widely distributed in human tissues and abnormally expressed in a va- riety of malignant tissues played an important role in tumor migration, adhesion and metastasis formation process. Firstly, the stable overexpression of Lumican in lung adenocarcinoma cell line A549 was estab- lished in the study. Furthermore, transwell chambers assay, adhesion, angiogenesis and animal experiments were used to detect the ability of invasion, migration, angiogenesis, homogeneous and heterogeneous cells intercellular adhesion among each group, and to investigate the effect of the metastasis on A549. Finally, Western blot was used to detect the expression of RhoC, p-Akt, MMP-2 and VEGF proteins in order to il- lustate the possible mechanism. Compared with the control group and （or） the empty vector group, the re- sults showed that the experimental group cells invasion and migration ability were enhanced （P〈0.05） andhomogeneous cells intercellular adhesion were decreased. Meanwhile, heterogeneous cells intercellular adhesion was incresed （P〈0.05）; Angiogenesis capacity and the vascular density which was got from nude mice subcutaneous tumor were increased （P〈0.05）; The expression of RhoC, p-Akt, MMP-2 and VEGF were significantly rised （P〈0.05） and there were no differences between the control group and empty vector group （P〉0.05）. The study indicated that the overexpression of Lumican gene could promote the metastasis of lung adenocarcinoma cell A549 in vitro, and its mechanism might be related to the increased expression of the RhoC protein.