title: Metformin associated with photodynamic therapy--a novel oncological direction.
abstract: The aim of our study was to assess the effect of the combined treatment of Metformin (Metf) and 5, 10, 15, 20-tetra-sulfophenyl-porphyrin (TSPP)-mediated photodynamic therapy (PDT) on an in vivo tumour model. Wistar male rats were divided in 6 groups: group 1, treated with TSPP; groups 2 and 4 treated with TSPP and Metf, respectively, and irradiated 24h thereafter; group 3 was treated with Metf and the last two groups received the combined treatment, Metf administered prior (group 5) or after (group 6) irradiation. 72 h from the start of the treatment, tumour tissue was sampled for the investigation of oxidative and nitrosative stress. The apoptotic rate, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions and matrix metalloproteinases activities were also quantified. Malondialdehyde and glutathione levels were significantly elevated in the groups treated with combined therapy (p<0.05). Metf associated with TSPP-PDT reduced iNOS and COX-2 expressions and enhanced nitrotyrosine levels in both therapeutic regimens. Peroxynitrate formation and its cytotoxic effect on tumour cells were related to an elevated index of apoptosis and necrosis. Moreover, MMP-2 activity reached a minimum in the groups which received combined therapy. Our results confirmed that the association of Metf with PDT might prove a new and promising oncological approach.
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Nenu
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Tiberiu
authors.initials: T
authors.lastname: Popescu
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Mihaela D
authors.initials: MD
authors.lastname: Aldea
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Craciun
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Diana
authors.initials: D
authors.lastname: Olteanu
authors.affiliation: Departments of Radiobiology and Tumor Biology, Oncology Institute "Prof. I. Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Tatomir
authors.affiliation: Department of Pathology, Cluj-Napoca, University of Agricultural Sciences and Veterinary Medicine, 3-5 Calea Manastur, 400372 Cluj-Napoca, Romania; Department of Biomedical Sciences, Ross University School of Veterinary Medicine Basseterre, PO Box 334, Saint Kitts and Nevis.
authors.forename: Pompei
authors.initials: P
authors.lastname: Bolfa
authors.affiliation: National Research & Development Institute for Chemistry and Petrochemistry ICECHIM 202 Splaiul Independentei, 060021 Bucharest, Romania.
authors.forename: Rodica M
authors.initials: RM
authors.lastname: Ion
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania.
authors.forename: Adriana
authors.initials: A
authors.lastname: Muresan
authors.affiliation: Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006 Cluj-Napoca, Romania. Electronic address: gabriela.filip@umfluj.ro.
authors.forename: Adriana G
authors.initials: AG
authors.lastname: Filip
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D009569:Nitric Oxide; C016136:tetraphenylporphine sulfonate; D008315:Malondialdehyde; D008687:Metformin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005978:Glutathione
keywords: Cancer; Metformin; Photodynamic therapy; TSPP