CD133陽性肺がん幹様細胞はPRDX5を介した抗酸化防御によりプラズマ活性化培地に対する耐性を示す

Plasma-activated medium (PAM), which generates reactive oxygen and nitrogen species (RONS), has emerged as a promising anti-cancer approach. However, although PAM effectively eliminates bulk tumor cells, surviving populations often acquire enhanced stem cell-like properties, suggesting selective resistance in cancer stem cells (CSCs). This study aimed to elucidate the molecular mechanisms underlying CSC resistance to PAM-induced oxidative stress in non-small cell lung cancer (NSCLC).

CD133⁺ and CD133^- subpopulations were isolated from A549 lung cancer cells to evaluate their sensitivity to PAM-induced cytotoxicity. Intracellular reactive oxygen species (ROS) levels, apoptosis, and antioxidant defense mechanisms were assessed in vitro, while therapeutic efficacy was examined using xenograft mouse models.

CD133⁺ A549 cells exhibited marked resistance to PAM-induced apoptosis compared with CD133^- cells, accompanied by significantly reduced intracellular ROS accumulation. Peroxiredoxin 5 (PRDX5) was identified as a key antioxidant enzyme that was highly up-regulated in CD133⁺ cells and essential for maintaining redox homeostasis. Genetic silencing of PRDX5 in CD133⁺ cells significantly enhanced PAM-mediated cytotoxicity both in vitro and in vivo, restoring sensitivity to oxidative damage. Furthermore, combining PRDX5 knockdown with PAM treatment or co-administering PAM with paclitaxel substantially suppresses tumor growth in xenograft models, reducing tumor burden and inflammatory responses. These findings reveal PRDX5 as a key survival factor enabling CSCs to evade plasma therapy and suggest that targeting PRDX5 alongside PAM or conventional chemotherapy could improve treatment outcomes in NSCLC.

PRDX5 plays a central role in mediating oxidative stress resistance in CD133⁺ lung cancer stem-like cells, enabling their survival following PAM treatment. Targeting PRDX5, either alone or in combination with PAM or conventional chemotherapy, represents a promising strategy to overcome cancer stem cell-mediated resistance and improve therapeutic outcomes in non-small cell lung cancer.