In Vivo Metabolic Analysis of the Anticancer Effects of Plasma-Activated Saline in Three Tumor Animal Models

Abstract

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.

Exploring animal models in oral cancer research and clinical intervention: A critical review

“…In addition, IHC staining showed that PAS-injected treatment reduced the number of Ki-67-positive tumour cells (Figure 4e,f), suggesting that PAS-injected treatment inhibits OTSCC growth (Qi et al, 2022).…”

“…This result, obtained by comparing PAS with saline in vivo, further emphasizes antitumour properties of PAS. In addition, IHC staining showed that PAS‐injected treatment reduced the number of Ki‐67‐positive tumour cells (Figure 4e,f ), suggesting that PAS‐injected treatment inhibits OTSCC growth (Qi et al., 2022 ).…”

“…H&E stain and Ki-67 stain are used to show tumour sections (e) at the top of the figure. Ki67-positive cells were analyzed quantitatively by Image J (f)(Qi et al, 2022(Qi et al, ). et al, 2017.…”

Editorials for ‘Advances in Cold Plasma in Biomedicines’

“…As a review by Kim et al in this Special Issue introduced, there have been many studies conducted elucidating the beneficial role of PAL for treating cancer. The research article by Kong et al described the anticancer effects of PAL using three tumor animal models [ 5 ]. In this study, saline was subjected to a treatment that used a device to generate plasma using ambient air.…”

Controlling plasma‐activated solution chemistry for targeted cancer cell death

“…[ 30 ] A recent study by Xu et al found that the addition of plasma‐treated saline to the cell culture medium could enhance the drug sensitivity of cancer cells, thereby facilitating cancer treatment. [ 31 ] Qi et al confirmed that plasma‐activated saline could effectively depress melanoma growth, [ 32 ] and plasma‐treated phosphate‐buffered saline has been evidenced to inhibit the growth of pancreatic cancer cells. [ 33 ] At the same time, it has been shown that plasma‐treated phosphate‐buffered saline can reduce immunosuppressive protein CD47 expression, thereby accelerating the demise of cancer cells.…”