Cold Atmospheric Plasma Treatment for Pancreatic Cancer–The Importance of Pancreatic Stellate Cells

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with low five-year survival rates of 8% by conventional treatment methods, e.g., chemotherapy, radiotherapy, and surgery. PDAC shows high resistance towards chemo- and radiotherapy and only 15–20% of all patients can have surgery. This disease is predicted to become the third global leading cause of cancer death due to its significant rise in incidence. Therefore, the development of an alternative or combinational method is necessary to improve current approaches. Cold atmospheric plasma (CAP) treatments could offer multiple advantages to this emerging situation. The plasma-derived reactive species can induce oxidative damage and a cascade of intracellular signaling pathways, which could lead to cell death. Previous reports have shown that CAP treatment also influences cells in the tumor microenvironment, such as the pancreatic stellate cells (PSCs). These PSCs, when activated, play a crucial role in the propagation, growth and survival of PDAC tumors. However, the effect of CAP on PSCs is not yet fully understood. This review focuses on the application of CAP for PDAC treatment and the importance of PSCs in the response to treatment.

Cold Physical Plasma in Cancer Therapy: Mechanisms, Signaling, and Immunity

“…The first report of using plasma in oncology was published in 2007 by showing the inactivation of melanoma cells in vitro following plasma treatment [ 14 ]. After that, more studies provided evidence of the anticancer capacity of plasma in several cancer types such as the brain [ 23 – 25 ], skin [ 26 – 29 ], breast [ 30 – 34 ], colorectal [ 35 – 37 ], lung [ 38 – 40 ], cervical [ 41 – 43 ], leukemia [ 44 – 48 ], pancreatic [ 49 – 54 ], liver [ 55 – 57 ], and head and neck [ 58 – 60 ]. Because of altered metabolism and mitochondrial dysfunction, cancer cells are often found to produce more intracellular ROS than nonmalignant cells [ 61 – 63 ].…”

Intracellular Responses Triggered by Cold Atmospheric Plasma and Plasma-Activated Media in Cancer Cells

“…A strong anti-proliferative effect of CAP/PAM was demonstrated in chondrosarcoma CAL-78, SW1353 [ 48 ], A549, H1299 [ 71 ], U-2 OS MNNG cells, 3T3 fibroblasts, HaCaT keratinocytes [ 79 ], glioblastoma cells [ 29 ], pancreatic cancer cells [ 80 ], MG63 osteosarcoma cells [ 57 , 81 ], and C2C12 myoblasts [ 82 ]. In this respect, CAP-treated osteosarcoma cells exhibit an increase of PRX 1 and ratio change of oxidized to reduced forms of PRX1 and PRX2, with an increased cellular concentration of oxidized dimer.…”

Novel Anticancer and Treatment Sensitizing Compounds against Pancreatic Cancer

“…Furthermore, an upregulation of ROS was identified in both the pancreatic cancer and stellate cells [57]. The application of plasma as an anticancer target for PDAC is very much in its infancy, however, this method may hold potential as a monotherapeutic and or/adjuvant target [58].…”