Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell...

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Photodynamic therapy (PDT) is an emerging cancer treatment modality.
• Novel photosensitizers are crucial for enhancing PDT efficacy.
• Understanding the molecular mechanisms of PDT is essential for its clinical application.

Purpose of the Study:

• To investigate the antitumor effects of a novel photosensitizer, meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP), mediated photodynamic therapy (DTP-PDT).
• To elucidate the underlying mechanisms of DTP-PDT, including its impact on cell viability, reactive oxygen species (ROS) generation, apoptosis, autophagy, and gene expression.

Main Methods:

• Cell viability was assessed using the Cell Counting Kit-8 assay.
• ROS generation was measured using the DCFH-DA fluorescent probe.
• Apoptosis was evaluated via Hoechst staining and western blotting for apoptosis-related proteins (Bax, Bcl-2).
• Autophagy was monitored by assessing LC3B-II levels.
• RNA sequencing and subsequent bioinformatic analyses (GO, KEGG, Disease Ontology, Reactome, PPI) were performed to identify differentially expressed genes and pathways.

Main Results:

• DTP-PDT significantly inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cancer cell lines.
• DTP-PDT-induced cytotoxicity was attenuated by a ROS scavenger (NAC) and a P38 MAPK inhibitor (SB203580).
• Apoptosis was induced by DTP-PDT, evidenced by altered Bax/Bcl-2 ratios, and this effect was also sensitive to NAC and SB203580.
• DTP-PDT increased the level of LC3B-II, indicating induction of autophagy.
• RNA sequencing identified 3496 differentially expressed mRNAs, enriched in pathways related to cell cycle, ribosomes, DNA replication, and protein binding, with cdk1 and rps27a identified as key interacting genes.

Conclusions:

• DTP-PDT demonstrates significant antitumor activity by inhibiting cell proliferation and inducing apoptosis and autophagy.
• The mechanisms involve ROS generation and activation of the P38 MAPK signaling pathway.
• Key molecular changes induced by DTP-PDT are associated with cell cycle regulation, ribosomal function, DNA replication, and protein binding, offering potential therapeutic targets.