Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells

• Published in: Photodiagnosis and photodynamic therapy 2019-12, Vol.28, p.88-97
• Main Authors: Doustvandi, Mohammad Amin, Mohammadnejad, Fateme, Mansoori, Behzad, Tajalli, Habib, Mohammadi, Ali, Mokhtarzadeh, Ahad, Baghbani, Elham, Khaze, Vahid, Hajiasgharzadeh, Khalil, Moghaddam, Mahsa Maleki, Hamblin, Michael R., Baradaran, Behzad
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Autophagy - drug effects; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Combination therapy; Diode laser; Dose-Response Relationship, Radiation; Doxorubicin; Doxorubicin - pharmacology; Drug Synergism; Humans; Indoles - pharmacology; Lasers, Semiconductor; Melanoma; Melanoma - drug therapy; Organometallic Compounds - pharmacology; PDT; Photochemotherapy - methods; Photosensitizing Agents - pharmacology; SK-MEL-3 cell line; Skin Neoplasms - drug therapy; Synergism; Zinc phthalocyanine
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2019.08.027

[Display omitted] •Photodynamic therapy with ZnPc (ZnPc-PDT) inhibits SK-MEL-3 cancer cells proliferation.•Pre-treatment with ZnPc-PDT, in low dose of laser, sensitizes SK-MEL-3 cells towards very lower concentration of Doxorubicin.•Combined ZnPc-PDT with DOX (chemo-photodynamic therapy) decreases cell viability synergistically.•Chemo-PDT decreases cell migration and increases rate of apoptosis, autophagy, cell cycle arrest at subG1 and G2-M phase. Chemotherapy is a generally used anticancer strategy for melanoma and it may have improved outcomes in combination with other approaches. One such strategy is photodynamic therapy (PDT), where a photosensitizer (PS) generates reactive oxygen species (ROS) after illumination of target cells. Interestingly, in low doses and high doses of light sources, special cellular responses can be induced. Regarding this fact, in this study, the combination of zinc phthalocyanine (ZnPc)-PDT and Doxorubicin (DOX) was applied at low and high dose of diode laser to treat SK-MEL-3 cells. Cytotoxic effects were determined by MTT assay for assessment synergistic effects were estimated by calculation of Combination Index (CI); that synergistic effects were observed in most groups. In low dose of laser irradiation higher synergism effects were observed. Significant changes of ROS were not observed with combinations, but autophagy, subG1 and G2/M phase cell cycle arrest, decreased cell migration ability and apoptosis induction were significantly increased compared to either treatment alone. The expression of caspase-8, -9, -3 and Bcl-2 genes revealed caspase-dependent apoptosis in all groups. Moreover, ZnPc-PDT and chemo-PDT down-regulated the expression of MMP-9 and Vimentin genes that impaired cell migration. In conclusion, it can be suggested that pre-treatment with ZnPc-PDT has high effects to sensitize SK-MEL-3 cells to DOX, in particular with low dose of diode laser.