BL-DVDMS-mediated photodynamic therapy induces oxidative response associated with cellular senescence via p53/GADD45A signaling in lung cancer

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Current chemotherapy options for lung cancer (LC) are limited by poor tumor selectivity, systemic toxicity, and acquired resistance. Photodynamic therapy (PDT) offers a promising minimally invasive modality as a potential conservative or complementary approach, yet its clinical adoption has been constrained by suboptimal photosensitizers and unclear mechanisms. This study investigated a novel PDT regimen combining a 450 nm blue laser with the photosensitizer sinoporphyrin sodium (DVDMS) to address these limitations in LC. Our findings demonstrate that BL-DVDMS treatment selectively inhibits lung cancer cell proliferation while sparing normal bronchial epithelial cells. Low-dose PDT induces a moderate oxidative stress response, leading to DNA damage and G2/M cell cycle arrest. Importantly, this treatment triggers a senescence-associated phenotype, evidenced by increased SA-β-Gal activity and elevated secretion of SASP factors (IL-6, IL-8), accompanied by altered p53/GADD45 A signaling. These effects are abrogated by ROS scavenging or p53 inhibition, indicating that the oxidative response plays a central role in the observed antitumor activity. In the subcutaneous xenograft model, this regimen significantly suppresses tumor growth with no detectable systemic toxicity. Collectively, this work identifies BL-DVDMS-mediated PDT as a mechanistically defined, senescence-associated therapeutic strategy. This study provides a potential complementary treatment option for inoperable LC patients, particularly for managing residual disease and enhancing existing therapies.