Targeted Overexpression of NDRG2 using Survivin Promoter Reduces Viability and Invasiveness of A549 Cell Line

Background: anti-tumor effects of n-myc downstream regulated gene2 (ndrg2) have been demonstrated in many tumors. in the present study, ndrg2 was specifically overexpressed in lung cancer cell line using survivin promoter (sur-p). then, the effects of ndrg2 overexpression on viability, apoptosis, migration, and invasion of a549 cells were evaluated. methods: recombinant padenovator-sur-p-ndrg2-ires-gfp plasmid harboring ndrg2 gene under transcriptional control of sur-p and mock plasmid were constructed. a549 lung tumor cells and lx-2 cells (non-tumor cell line) were transfected with padenovator-sur-p-ndrg2-ires-gfp, padenovator-cmv-ndrg2-ires-gfp, or mock plasmids. tumor specificity of sur-p was evaluated using fluorescent microscopy for gfp expression. the effects of ndrg2 overexpression on cell viability, apoptosis, and migration of a549 cells were measured using mtt, annexinv/7-aad flow cytometry, and transwell migration assay, respectively. ndrg2 and matrix metalloproteinase- 2 (mmp-2) expression were measured using real time- pcr. results: padenovator-sur-p-ndrg2-ires-gfp transfection resulted in a huge gfp expression in a549 cells, but not in lx-2 cells. the results of real time-pcr analysis also showed that padenovator-sur-p-ndrg2-ires-gfp transfection led to an abundant ndrg2 expression in a549 cells. ndrg2 overexpression decreased a549 cell viability through increasing cell apoptosis. in addition, migration, invasion, and mmp-2 expression decreased following ndrg2 overexpression in a549 cells. conclusion: the findings indicate that the targeted overexpression of ndrg2 using sur-p can reduce the viability and invasiveness of a549 cells, suggesting possible benefits of this approach in lung cancer therapy.