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2017 ; 14
(1
): 1049-1053
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Metformin enhances the cytotoxicity of 5-aminolevulinic acid-mediated
photodynamic therapy in vitro
#MMPMID28693272
Osaki T
; Yokoe I
; Takahashi K
; Inoue K
; Ishizuka M
; Tanaka T
; Azuma K
; Murahata Y
; Tsuka T
; Itoh N
; Imagawa T
; Okamoto Y
Oncol Lett
2017[Jul]; 14
(1
): 1049-1053
PMID28693272
show ga
The biguanide metformin is a drug widely used for the treatment of type 2
diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the
adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling
pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA), a
precursor of protoporphyrin IX (PpIX), leads to apoptosis when PpIX accumulates
in the mitochondria, and also leads to autophagy through activation of AMPK. In
the present study, the effect of metformin in combination with 5-ALA-PDT was
evaluated in vitro in KLN205 lung cancer cells. At a fluence of 5 J/cm(2),
5-ALA-PDT in combination with 5 mM metformin exhibited significantly increased
cytotoxicity compared with that observed with 0 and 0.1 mM metformin (P=0.0197
and P=0.0423, respectively). The cells treated with 5-ALA-PDT and metformin
exhibited condensation of nuclear chromatin and the presence of autophagosomes.
These results indicate that apoptosis and autophagy occur in KLN205 cells
following combined treatment with 5-ALA-PDT and metformin. The results from the
present study are the first to indicate, to the best of our knowledge, that
metformin potentiates the efficacy of 5-ALA-PDT.