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/cm2, 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.