TY - JOUR
T1 - Metformin associated with photodynamic therapy - A novel oncological direction
AU - Nenu, Iuliana
AU - Popescu, Tiberiu
AU - Aldea, Mihaela D.
AU - Craciun, Lucian
AU - Olteanu, Diana
AU - Tatomir, Corina
AU - Bolfa, Pompei
AU - Ion, Rodica M.
AU - Muresan, Adriana
AU - Filip, Adriana G.
PY - 2014/9/5
Y1 - 2014/9/5
N2 - 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 24 h 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.
AB - 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 24 h 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.
KW - Cancer
KW - Metformin
KW - Photodynamic therapy
KW - TSPP
UR - http://www.scopus.com/inward/record.url?scp=84902199359&partnerID=8YFLogxK
U2 - 10.1016/j.jphotobiol.2014.04.027
DO - 10.1016/j.jphotobiol.2014.04.027
M3 - Article
C2 - 24911275
AN - SCOPUS:84902199359
SN - 1011-1344
VL - 138
SP - 80
EP - 91
JO - Journal of Photochemistry and Photobiology B: Biology
JF - Journal of Photochemistry and Photobiology B: Biology
ER -