Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells.
OBJECTIVE
We investigated the effects of photodynamic therapy (PDT) combined with low-dose chemotherapy on breast cancer cells. Photodynamic treatment was administered by irradiating indocyanine green-preloaded MCF-7 cells with an IR diode laser source at 805 nm; cisplatin was used for chemotherapy.


METHODS
The dose-response phenomena associated with the two treatments administered individually and together were evaluated with the following tests: trypan blue dye exclusion, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic survival, thymidine and methionine incorporation, and insulin-dependent and insulin-independent glucose transport.


RESULTS
Viability and metabolic data demonstrated mutual reinforcement of therapeutic efficacy. However, isobolographic analysis of quantal and variable data indicated that reinforcement was additive according to trypan blue data and synergistic according to MTT data. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, we evaluated (by Western blotting) the expression of proteins Bcl-2, Bax, Bcl-X(L), p21, p53, and poly(ADP-ribose) polymerase. Photodynamic treatment caused transient selective destruction of Bcl-2 and up-regulation of Bax. It also induced apoptosis in a limited fraction of cells (10-12%). Flow cytometry data showed that PDT killed mostly G(1)-phase cells, whereas cisplatin killed mostly S-phase cells. This disjointed phase-related effect may account for the favorable effects exerted by combined treatment.


CONCLUSIONS
Our findings imply that low doses of cytostatic drugs may be as effective or even more effective than currently used doses if appropriately combined with PDT.
Crescenzi
Elvira
E
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, University of Naples, Federico II, Naples, Italy.
Varriale
Linda
L
Iovino
Mariangela
M
Chiaviello
Angela
A
Veneziani
Bianca Maria
BM
Palumbo
Giuseppe
G
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage / Q000494:pharmacology*; D010778:Photochemotherapy; D014176:Protein Biosynthesis / Q000187:drug effects
D000970:Antineoplastic Agents; D004247:DNA; D007208:Indocyanine Green; D005947:Glucose; D002945:Cisplatin