Plasma‐Activated Medium Inhibits Tumor Growth in Patient‐Derived Organoids and Xenograft Models of Colorectal and Lung Cancer

ABSTRACT The application of cold atmospheric plasma (CAP) and its derivative plasma‐activated medium (PAM) represents a promising approach for cancer therapy. However, conventional 2D cultures fail to recapitulate the structural complexity and heterogeneity of native tumors. In this study, we established patient‐derived organoids (PDOs) and patient‐derived xenograft (PDX) models to assess the antitumor efficacy of PAM. PAM inhibited PDO growth, disrupted organoid architecture, increased cytotoxicity, and induced intracellular ROS accumulation. Mechanistically, PAM activated apoptosis‐related signaling, including p53, Bax, Bak, and cleaved caspase‐3, while reducing Bcl‐2 expression. In PDX tumors, PAM suppressed tumor growth, decreased Ki‐67 staining, and increased p53 and cleaved caspase‐3 expression. These findings provide clinically relevant patient‐derived evidence supporting PAM as a potential translational antitumor or adjunct therapeutic strategy.