Synergistic Enhancement of Apoptosis by Protoporphyrin IX-Mediated Sono-Photodynamic Therapy in HepG2 Hepatocellular Carcinoma Cells

Authors : Adem Yavaş, Mehran Aksel

Pages : 13-22

Doi:10.20515/otd.1752148

View : 91 | Download : 176

Publication Date : 2025-12-15

Article Type : Research Paper

Abstract :Hepatocellular carcinoma (HCC) lacks effective therapies at advanced stages. This study aimed to evaluate the cytotoxic and pro-apoptotic effects of Protoporphyrin IX (PpIX)-mediated sonodynamic (SDT), photodynamic (PDT), and combined sono-photodynamic therapy (SPDT) on HepG2 cells. HepG2 cells were treated with 50 µM PpIX alone or combined with SDT (1 MHz, 0.5 W/cm², 60 s), PDT (630 nm, 2 mJ/cm², 30 s), or sequential SPDT. Viability (MTT), oxidative stress (TOC, TAC), apoptosis (Annexin V-FITC/PI staining), and apoptotic protein expression (Bax, Bcl-2, cleaved caspase-3, -9 via Western blot) were assessed.PpIX alone showed no cytotoxicity (p > 0.05). SDT and PDT significantly reduced viability by 24.33% (p < 0.05) and 43.33% (p < 0.01), respectively, while SPDT reduced it by 83.33% (p < 0.001). TOC levels increased significantly in SDT and PDT groups (p < 0.01), peaking in SPDT (p < 0.001). Apoptosis rates were highest with SPDT (p < 0.001 vs. all). SPDT markedly upregulated Bax and cleaved caspases while downregulating Bcl-2 (p < 0.001).PpIX-mediated SPDT induces synergistic cytotoxicity in HepG2 cells through enhanced oxidative stress and activation of mitochondrial apoptosis pathways. These findings suggest SPDT as a promising strategy for HCC treatment, warranting further preclinical investigation.
Keywords : Protoporfirin IX, Hepatoselüler karsinom, Sonodinamik tedavi, Fotodinamik tedavi, Apoptoz, Oksidatif stres

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