PNAS: Low temperature atmospheric plasma (CAP) "gas" for leukemia treatment?

Treatment resistance/resistance is a rather thorny problem faced by tumor clinical treatment

In recent years, cellular reactive oxygen species (ROS) have been found to be abnormally elevated in tumor cells and are closely related to glycolysis, redox, and proliferative signaling, suggesting that it may be this shared “weakness”

In 2021, a research team from Xi'an Jiaotong University, Old Dominion University, and the University of Utah found that in a mouse model of drug-resistant chronic myeloid leukemia (CML), the CAP treatment regimen it developed could effectively block oxidative stress, including oxidative stress.

Research results (Source: PNAS Magazine)

The main problem with existing ROS therapies is the inability to determine the effective concentration of ROS: too low ROS levels cannot induce apoptosis, and too high ROS levels activate the cancer-promoting HIF-α pathway

Tri-CAP treatment of cell-free medium (Image source: PNAS Magazine)

The intracellular level of ROS in drug-resistant CML cells was higher after Tri-CAP treatment (Image source: PNAS Magazine)

The researchers further found that low levels of ROS stimulated by Tri-CAP disrupted the redox balance in cells

Redox imbalance in resistant and sensitive CML cells after Tri-CAP treatment (Source: PNAS Magazine)

The study also found that Tri-CAP can also inhibit multiple key targets in tumor metabolism and reduce lactate production

Glycolysis of drug-resistant CML was inhibited after Tri-CAP treatment (Source: PNAS Journal)

Lactic acid, the product of aerobic glycolysis, is one of the activators of PI3K/AKT/mTOR, the main tumor proliferation pathway.

The drug-resistant CMLAKT/mTOR/HIF-1α pathway was activated after Tri-CAP treatment (Source: PNAS Journal)

Taken together, these results demonstrate that Tri-CAP can preferentially block three critical pathways of cancer survival in redox homeostasis, glycolysis and proliferation (AKT/mTOR/HIF-1α) in resistant CML, revealing for the first time a previously Unreported cancer treatments

In addition, Tri-CAP can induce apoptosis of drug-resistant cells

Tri-CAP-treated tumor-bearing mice had reduced tumor growth and prolonged survival (Source: PNAS Journal)

Conventional ROS-generating therapies, including radiotherapy, usually rely on high levels of ROS to induce direct cancer cell death, but at the same time, tumor survival-related pathways are activated, resulting in limited efficacy

Original source:

Guo B, Pomiter AD, Li F, Bhatt S, Chen C, Li W, Qi M, Huang C, Deininger MW, Kong MG, Chen HL.