Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells

Abstract

Background: Cytotoxic, antiproliferative, cell cycle inhibitive, oxidative and apoptotic effects of cetuximab [antibody for epidermal growth factor receptor (EGFR)] alone and together with stabilized silver ion solution (St-Ag) on P-H1299, R-H1299, A-431 and A-549 cells were investigated.

Materials and methods: Cytotoxic effects of cetuximab alone and together with St-Ag on cells were determined by Cell Titer-Blue((R)) Cell Viability and Lactate Dehydrogenase Activity tests. Cell cycle distributions and apoptosis were detected by reverse transcription polymerase chain reaction (RT-PCR).

Results: St-Ag enhanced cetuximab cytotoxic effect on all cells. LDH activity, as a result of cell death, was found the highest level at treatment of cetuximab with St-Ag in all cells. Both treatment increased caspase-3/7 activity which is apoptotic enzyme was found higher in A-549 cells than other cells. Also, treatment of cetuximab with St-Ag caused increasing Bax/Bcl-2 ratio in all cells. Cetuximab with St-Ag treatment increased glutathione peroxidase activity in all cells generating oxidative stress. Proliferating Cell Nuclear Antigen (PCNA), topoisomerase II-alpha (except R-H1299), cyclin D1 and D2 genes expression were decreased in all cells which explain the cell cycle inhibition effect.

Conclusion: These findings suggest that treatment of cetuximab combined with St-Ag exhibit more carcinogenesis reducing potential than cetuximab alone.