Magnetic Nanoparticles Mediated Wild-type PTEN Gene Transfection To Cisplatin-resistant Lung Adenocarcinoma And Its Effect On Growth And Chemotherapy Resistance

Objective To evaluate the transfection efficiency,sustained expression and toxicity of polyethyleneimine(PEI) coated magnetic iron oxide nanoparticles(polyMAG-1000) as gene vectors.To study the effect of wild-type PTEN gene on anti-proliferative activity and its efficiency of reversing resistance in cisplatin-resistant lung adenocarcinoma cell line A549/DDP.Methods 1.The plasmid containing wild-type PTEN was transfected into cisplatin-resistant lung adenocarcinoma cell lines A549/DDP mediated by polyMAG-1000 and Lipofactamine 2000 respectively.The efficiency of transfection was analyzed by fluorescent microscope and flow cytometry.The mRNA and protein of cells were measured by RT-PCR and immunocytochemical staining.The toxicity of delivery systems was measured by MTT.2.The survival rate and the resistance to cisplatin of cells were measured by MTT.Flow cytometry was used to analyze the cell cycle and apoptosis.Results 1.The efficiency of transfection mediated by polyMAG-1000(52.22±2.41)%was higher than mediated by Lipofactamine 2000(32.15±3.13)%.Cells transfected with polyMAG-1000 showed a sustained increased PTEN gene level while with Lipofactamine 2000 showed a decrease.There was no significant toxicity of delivery systems at a concentration of 2μl/ml and 4h incubation time.2.Cell lines that transfected by wild-type PTEN had a lower cell survival rate,a higher proportion of cells in G1 phase and an increase in the rate of apoptosis.The IC50 and resistance index to cisplatin were down-regulated in cells transfected with wild-type PTEN. All these effects were greater in cells transfected mediated by polyMAG-1000 than mediated by Lipofactamine 2000.Conclusion 1.PolyMAG-1000 could be one of favored gene carriers for PTEN gene delivery with a sustained and significantly efficient gene expression.There was no significant toxicity of delivery systems at the concentration and incubation time of transfection.2. Wild-type PTEN transfer could inhibit the growth of cisplatin-resistant lung adenocarcinoma cell line A549/DDP and this effect was possibly attributed to inducement of cell cycle arrest at G1 phase and cell apoptosis.Wild-type PTEN transfer could resulted in a reversal effect of cisplatin resistance in cisplatin-resistant lung adenocarcinoma cell line A549/DDP.