title: Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and in vivo.
abstract: BACKGROUND
  The treatment of pancreatic cancer has remained dismal despite advances in medical and surgical care. Recent preclinical data have revealed that hypericin, a photochemical dye, is activated by green light and generates toxic radical species in tumors. We hypothesized that interstitial hypericin and laser phototherapy would decrease pancreatic cancer growth.
  
  
  METHODS
  MiaPaCa-2 and PANC-1 cells were grown in tissue culture. In vitro experiments were performed with addition of 10 microg of hypericin/500,000 cancer cells. Cells were incubated with hypericin for 2 h. Cells were then exposed to KTP532 green laser light for 1 min at 0.6 W using a cylindrical diffuser tip. Cell growth was measured by MTT assay 24 h after laser treatment, N = 12. MiaPaCa-2 cells were implanted subcutaneously and orthotopically in pancreas of nude mice. After 5 weeks, both tumors were injected with 100 microg of hypericin followed by insertion of a cylindrical diffuser tip into the tumor center. Mice received 200J KTP laser light at 1.0 W in two sites. Tumors were measured before and 4 weeks after laser treatment.
  
  
  RESULTS
  Both in vitro and in vivo mice data showed a significant decrease in growth of pancreatic cancer. Pancreatic cancer cell growth was suppressed by 66.1 +/- 0.2%, n = 12, P < 0.01, ANOVA. Subcutaneous shoulder tumors were suppressed by 91.2 +/- 2.3%, n = 12, P < 0.001, and orthotopically grown pancreatic tumors were suppressed by 42.2 +/- 8.1%, n = 12, P < 0.05, compared to pretreatment sizes. Data expressed as percentage reduction vs paired controls in the MTT assay and vs pre-photodynamic therapy in mice experiments. Paired Student's t tests were performed vs pretreatment sizes.
  
  
  CONCLUSIONS
  Both in vitro and in vivo results revealed a significant decrease in pancreatic cancer cell growth. Laser or dye alone had no effect, indicating that intratumor hypericin and laser therapy may prove useful in unresectable pancreatic cancer.
authors.affiliation: Department of Surgery, UCLA Medical Center, Los Angeles, California 90095-6904, USA. cdliu@mednet.ucla.edu
authors.forename: C D
authors.initials: CD
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Kwan
authors.forename: R E
authors.initials: RE
authors.lastname: Saxton
authors.forename: D W
authors.initials: DW
authors.lastname: McFadden
mesh_terms: D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010778:Photochemotherapy; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D010569:Perylene; C004965:hypericin