Effect of dimethyl amiloride on invasive activity of highly-metastatic lung carcinoma cell line and its possible mechanisms
10.3781/j.issn.1000-7431.2009.12.001
- VernacularTitle:二甲基阿米洛利对高转移性肺癌细胞侵袭能力的影响及其作用机制
- Author:
Bin XU
;
Jingwen SHI
;
Jianwen MAO
- Publication Type:Journal Article
- Keywords:
Lung neoplasms;
Neoplasm metastasis;
Neoplasm invasiveness;
Urinary plasminogen activator;
Tumor cells;
cultured;
Dimethyl amiloride
- From:
Tumor
2009;(12):1107-1111
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of dimethyl amiloride (DMA) on invasive activity of PGCL3 cells from a human highly-metastatic lung carcinoma cell line in vitro and elucidate its possible mechanism. Methods:The invasion and migration capacities of PGCL3 cells were measured by using Transwell chamber assay after pretreatment with DMA. The effects of DMA on the activity of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) secreted by PGCL3 cells were measured by chromogenic substrate assay. The effects of DMA on uPA, urokinase-type plasminogen activator receptor (uPAR), and PAI-1 mRNAs transcription were determined by RT-PCR. The expression levels of extracellular regulated protein kinases 2 (ERK2) and ras protein were assessed by Western blot. Results:DMA inhibited invasion and migration capabilities of PGCL3 cells in vitro, down-regulated the mRNA transcription of uPA, uPAR and PAI-1, as well as up-regulated the expression of ras protein. After 24-hour treatment, DMA reduced the activity of uPA at higher concentration, but DMA had no effects on the activity of secreted PAI-1 protein and expression of ERK2 protein. Conclusion:DMA inhibits the invasion and migration of highly-metastatic lung cancer PGCL3 cells. The mechanism might be associated with down-regulation of the expression of uPA system.
