ALA-PDT results in phenotypic changes and decreased cellular invasion in surviving cancer cells.
OBJECTIVE
The mechanisms of photodynamic therapy (PDT) have been studied on the cellular and tissue levels. However, the cellular behaviors of cancer cells survived from PDT are still not clear. This study attempted to investigate the influence of 5-aminolevulinic acid (ALA)-based PDT on the invasion ability as well as molecular changes in surviving cancer cells and their progeny.


METHODS
The systematic effects of ALA-PDT were evaluated using human invasive carcinoma cells (lung adenocarcinoma CL1-5 cells, melanoma A375 cells and breast carcinoma MDA-MB-231 cells). To study the cellular behaviors of surviving cancer cells, PDT-derived variants were established as stable cell lines after consecutive treatment with ALA-PDT. Scratch wound assay and invasion assay were performed to evaluate the migration and invasion ability in the surviving cancer cells and the established PDT-derived variants. RT-PCR and immunoblot analysis were performed to examine the expression levels of epidermal growth factor receptor (EGFR).


RESULTS
Though ALA-PDT caused differential phototoxicity among these invasive carcinoma cells, reduced migration was found in all the surviving cancer cells Compared to parental cancer cells, the established PDT-derived variants exerted significant phenotypic changes of cellular morphology, reduced mitochondrial function and a suppressed cellular invasiveness. Furthermore, correlated with the reduced invasion ability, expression of EGFR was downregulated in these established PDT-derived variants.


CONCLUSIONS
Except for direct cell killing, ALA-PDT could reduce EGFR expression and invasion ability of the surviving cancer cells and these effects could further pass to the progeny. The results from this study provide insights into a new mechanism by which PDT might affect cellular behaviors and tumor metastasis.
Tsai
Tsuimin
T
Graduate Institute of Biomedical Materials and Engineering, Graduate School of Dentistry, Taipei Medical University, Taipei 110, Taiwan.
Ji
Hong Tai
HT
Chiang
Pei-Chi
PC
Chou
Ruey-Hwang
RH
Chang
Wun-Shaing Wayne
WS
Chen
Chin-Tin
CT
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy; D008545:Melanoma / Q000473:pathology / Q000532:radiotherapy; D008928:Mitochondria / Q000528:radiation effects; D009361:Neoplasm Invasiveness / Q000235:genetics*; D010641:Phenotype; D010778:Photochemotherapy; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy; D014407:Tumor Cells, Cultured / Q000473:pathology* / Q000528:radiation effects*
D000622:Aminolevulinic Acid; D066246:ErbB Receptors