Interstitial Photodynamic Therapy Significantly Inhibits A549 Lung Adenocarcinoma Growth in Nude Mice

Lung adenocarcinoma, a prevalent and aggressive form of non-small cell lung cancer, often presents challenges in treatment due to resistance mechanisms and systemic toxicities of conventional therapies. While photodynamic therapy (PDT) offers a localized, minimally invasive approach, its efficacy can be limited by light penetration and photosensitizer distribution. Interstitial photodynamic therapy (IPDT) aims to overcome these limitations by directly delivering light into the tumor, potentially enhancing therapeutic outcomes and addressing the need for more targeted and effective treatments.

Twenty-four nude mice bearing human A549 lung adenocarcinoma xenografts were established and randomized into four equal groups: control, photosensitizer-only, laser-only, and IPDT. Each group received treatment according to its designation. Primary endpoints included monitoring tumor volume growth changes. Pathomorphological changes were observed via HE staining, and apoptosis was assessed using TUNEL assay. The expression levels of Survivin, Caspase-3, Bax, Bcl-2, VEGF, and HIF-1α genes in tumor tissues were quantified using qRT-PCR and Western blot assays.

The IPDT group exhibited noticeably smaller tumor volumes compared to the control, photosensitizer-only, and laser-only groups, with statistically significant differences (P < 0.05). HE staining of tumor tissues from the IPDT group revealed extensive necrotic, disordered, and foamy cells, contrasting sharply with the closely arranged, hyperchromatic cells observed in the other three groups. The TUNEL assay further confirmed that the IPDT group had a significantly higher number of apoptotic cells, characterized by brown nuclear particles. qRT-PCR and Western blot analyses demonstrated that, compared to the other three groups, IPDT significantly decreased the expressions of Survivin, Bcl-2, VEGF, and HIF-1α. > Concurrently, the expressions of Caspase-3 and Bax were significantly increased in the IPDT group (all P < 0.05), indicating a strong pro-apoptotic and anti-angiogenic effect.