Lung cancer is the leading cause of all cancer deaths, with estimates of 130,180 deaths and 236,740 new cases for 2022 in the United States [1]. Available treatments for non-small cell lung cancer include chemo- and immunotherapies which have undesirable side effects such as pain, flu-like symptoms, fatigue, hair loss, anemia, lymphedema, and appetite loss. Current treatments are also limited by toxicity to non-cancerous cells, drug resistance causing immunity to anti-cancer drugs, and length of treatment time. A goal of modern lung cancer treatments is to improve the quality of life given the current side effects. In this study, a novel approach to cancer treatment utilizing membrane electroporation (EP) and administration of cold atmospheric plasma (CAP) is explored. EP delivers electrical pulses to cells, opening pores in the cell membrane while CAP delivers reactive oxygen and nitrogen species at room temperature. The goal of this combination treatment is to take advantage of the disrupted oxidant-antioxidant balance and lowered ROS threshold of cancerous cells, delivering ROS to an apoptotic-inducing state, while causing relatively small damage to healthy cells [2]. In previous studies from Mazandaran University of Medicinal Science, it was observed that CAP administration to B16 melanoma and L929 normal breast tissue cell lines increased cell death in B16 cells and had no significant toxicity in L929 cells [3].
Human epithelial lung cancer cell line, A549, was used in this study. FITC-dextran 4 (FD4) was delivered to cells at varying time intervals with electroporation at various voltages and pulse durations to investigate A549 pore formation and optimal EP parameters. Cellular uptake of FD4 was quantified by fluorescence intensity. Next, cell viability by mitochondrial activity was evaluated following EP treatment and CAP delivery using MTT assay. Future work includes reactive oxygen species quantification, evaluation of cellular progression to apoptosis by caspase 3 activation, and inflammatory cytokine secretion.
[1] Howlader N, et al. National Cancer Institute. 2019.
[2] Krug, D, et al. EEE Transactions on Plasma Science. 2019.
[3] Motaln, H, et al. Molecules. 2021.
