Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin-resistant bladder cancer cell-line model.
OBJECTIVE
To investigate the hypothesis that sequential mitomycin C and 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant derivative, J82/MMC, and to assess the theoretical basis of this interaction by measuring the relative mitochondrial density of the respective cell lines, on the basis that the mitochondria are the intracellular site where ALA is metabolized to the active photosensitizer, protoporphyrin IX.


METHODS
Cell survival was assayed in J82 cell line and the J82/MMC derivative after treating them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123rhodamine fluorescence.


RESULTS
The effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated PDT was administered before mitomycin C, the combined effect was 'sub-additive'. 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter.


CONCLUSIONS
Mitomycin C appears to enhance ALA-mediated PDT when administered first. This appears to be particularly so in J82/MMC. This phenomenon may have clinical significance in recurrent superficial bladder cancer.
French
A J
AJ
Department of Urology, University Hospital of Wales, Heath Park, Cardiff, UK.
Datta
S N
SN
Allman
R
R
Matthews
P N
PN
D000622:Aminolevulinic Acid / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008928:Mitochondria; D016685:Mitomycin / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D017319:Photosensitizing Agents; D016685:Mitomycin; D000622:Aminolevulinic Acid