title: Synergistic increase in osteosarcoma cell sensitivity to photodynamic therapy with aminolevulinic acid hexyl ester in the presence of hyperthermia.
abstract: OBJECTIVE
  We observed that two osteosarcoma cell lines from the same tumor displayed marked differences in their sensitivities to photodynamic therapy (PDT) with aminolevulinic acid hexyl ester (hALA-PDT). We investigated why these two closely related lines had different hALA-PDT sensitivities and whether the PDT phototoxicity of the less sensitive cell line could be increased by a simultaneous application of hyperthermia (HT).
  
  
  METHODS
  Flow cytometry was used to evaluate the intracellular accumulation of protoporphyrin IX (PpIX), a metabolic product of aminolevulinic acid, in two human mandibular osteosarcoma cell lines (HOSM-1 and HOSM-2) treated with HT, hALA-PDT, or hALA-PDT combined with HT (PDT + HT). With hALA-PDT, cells treated with 0.2 mM hALA were irradiated with a light dose of 10-80 J/cm(2) from a near-infrared irradiator. With PDT + HT, the cells were treated as for hALA-PDT except that the temperature was raised to 43.5 degrees C during irradiation.
  
  
  RESULTS
  At 6 h after hALA treatment, HOSM-2 cells carried about 1.53-fold more PpIX than HOSM-1 cells. With hALA-PDT, the survival rate for HOSM-1 cells treated with 80 J/cm(2) irradiation was 35.7%, while that for HOSM-2 cells treated with 40-80 J/cm(2) was below 12%. With PDT + HT, the survival rate for HOSM-1 and HOSM-2 cells treated with 80 J/cm(2) irradiation was 14.1% and 10.7%, respectively.
  
  
  CONCLUSIONS
  A combination therapy comprising hALA-PDT + HT treatment may be very useful for the treatment of tumors containing cells that are insensitive to hALA-PDT, such as the HOSM-1 cell line described in this study.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Reparative and Regenerative Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan. shigeaki@clin.medic.mie-u.ac.jp
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Yanase
authors.forename: Jouji
authors.initials: J
authors.lastname: Nomura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Toshiro
authors.initials: T
authors.lastname: Tagawa
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced; D007259:Infrared Rays; D008339:Mandibular Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D012516:Osteosarcoma / Q000737:chemistry / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000032:analysis
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C419924:5-aminolevulinic acid hexyl ester