Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and in vivo.
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.
Liu
C D
CD
Department of Surgery, UCLA Medical Center, Los Angeles, California 90095-6904, USA. cdliu@mednet.ucla.edu
Kwan
D
D
Saxton
R E
RE
McFadden
D W
DW
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
D000873:Anthracenes; D000970:Antineoplastic Agents; D010569:Perylene; C004965:hypericin