BL-DVDMS-mediated photodynamic therapy induces oxidative response associated with cellular senescence via p53/GADD45A signaling in lung cancer
- 1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University
- 2Department of Urology, First Affiliated Hospital, Xi’an Jiaotong University
Abstract
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.
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BibTeX
@article{li2026bldvdmsmediated,
title = {{BL-DVDMS-mediated photodynamic therapy induces oxidative response associated with cellular senescence via p53/GADD45A signaling in lung cancer}},
author = {Xing Li and Minghai Ma and Yibo Mei and Pan Zhang and Xiao Liang and Rou Huang and Yuanquan Zhang and Dalin He and Lei Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1935296},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1935296/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - BL-DVDMS-mediated photodynamic therapy induces oxidative response associated with cellular senescence via p53/GADD45A signaling in lung cancer
AU - Xing Li
AU - Minghai Ma
AU - Yibo Mei
AU - Pan Zhang
AU - Xiao Liang
AU - Rou Huang
AU - Yuanquan Zhang
AU - Dalin He
AU - Lei Wang
PY - 2026
DA - 2026/10/28
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1935296
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1935296/full
AB - 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.
SN - 1663-9812
ER -