Effects Of Internalized Gold Nanoparticles On Cytotoxicity And Invasion In Lung Cancer Cells

Background Lung cancer is the most common malignant tumor of the elderly, which has become the leading cause of cancer-related death in our country. Invasion and metastasis are important pathological features of lung cancer cells. Currently treatments for lung cancer include surgery, radiotherapy and chemotherapy and so on. Recurrence rate of invasive lung cancer is extremely high after treatment, and there is no effective treatment. In recent years, the application potential of gold nanoparticles (AuNPs) has been greatly developed, which has made remarkable results in many fields such as targeted drug delivery, clinical examination, radiography imaging and cancer treatment. The instrinsic treatment of AuNPs has caused more and more attention. At present, the effect of unmodified AuNPs on invasive ability of lung cancer cells hasn’t been yet reported, and the size effect of AuNPs is unclear.Objective To explore the effects of internalized gold nanoparticles on cytotoxicity and invasion in lung cancer cells (A549and95D) and analyze the size effects and relative mechanisms.Methods The A549and95D cell culture medium were added5-nm,10-nm,20-nm, and40-nm gold nanoparticles solutions or not, respectively, incubated for24,48or72h. Characterization of AuNPs and its distribution in the cell were identified and observed by transmission electron microscopy (TEM); cell viability was tested using cell proliferation and toxicity detection kit; cell cycle and apoptosis were detected using flow cytometry; cell invasive ability was measured using transwell invasion assay and cell invasion fluorescence assay kit (ECM554); levels of invasion-related genes MMP9and ICAM-1mRNA were analyzed using RT-PCR; expression levels of invasion-related protein were analyzed using liquid chip method (Luminex technology) and Western blotting analysis.Results AuNPs showed as sphere with uniform size by TEM, AuNPs samples showed single sharp absorption peak by UV-visible spectroscopy; large number of AuNPs were seen in small vesicles, cytoplasm, lysosomes and perinuclear region in A549and95D cells; cell viability of A549and95D decreased significantly after treatment with5-nm AuNPs;5-nm AuNPs significantly increased apoptosis rate in95D; cell cycle of A549and95D processed obvious stagnation after treatment with5-nm AuNPs, in which G0/G1phase was significantly prolonged; the5-nm group of A549and10-nm group of95D were significantly enhanced in cell invasion, and the mRNA and protein expression levels of MMP9and ICAM-1were significantly increased in the two groups.Conclusions5-nm AuNPs could cause significant cytotoxicity in A549and95D.5-nm and10-nm AuNPs were able to promote cell invasion in A549and95D, respectively, which may be associated with upregulation of MMP9and ICAM-1. Particle size and cell type are vital factors affecting cell proliferation, apoptosis, cell cycle and invasion. This study provides a new understanding of AuNPs research on cytotoxicity and cell invasion, which has much indicative value for the AuNPs application of cancer therapy.