title: Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells.
abstract: 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.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, University of Naples, Federico II, Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Crescenzi
authors.forename: Linda
authors.initials: L
authors.lastname: Varriale
authors.forename: Mariangela
authors.initials: M
authors.lastname: Iovino
authors.forename: Angela
authors.initials: A
authors.lastname: Chiaviello
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Veneziani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004247:DNA; D007208:Indocyanine Green; D005947:Glucose; D002945:Cisplatin