Aminolevulinic acid-photodynamic diagnosis (ALA-PDD) is a promising alternative method to detect
cancer cells because of its high specificity and low rate of side effects. Exogenous ALA is administered and accumulates as
protoporphyrin IX (
PpIX) in
cancer cells, which then emit red fluorescence following light irradiation to enable surgeons to accurately identify and remove cancerous tissue. Recent reports suggested that
PpIX failed to accumulate in some patients who underwent ALA-PDD. We hypothesized that cell senescence, which is a relatively inactive state, affects
porphyrin accumulation in
bladder cancer cells. In this study, we evaluated the relationship between cell senescence and
porphyrin accumulation in affecting the efficacy of ALA-PDD. First, we utilized three
bladder cancer cell lines to evaluate senescence-related indicators and establish a cell senescence model. Then, we identified the differences in
porphyrin production and the
proteins involved in
porphyrin accumulation between old and young cells. We found that compared with young cells, old cells possessed higher concentration of
PpIX and had lower ABCG2 expression. The increase in
PpIX levels following ABCG2 inhibition is three times higher in old cells than in young cells, suggesting that cell senescence was closely related with
porphyrin accumulation in
cancer. In conclusion, we found that the efficacy of ALA-PDD and
porphyrin accumulation was relatively high in senescent
cancer cells and that inhibition of ABCG2 could improve the efficacy of ALA-PDD in young
bladder cancer cells.