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 reveale d that hypericin, a photochemical dye, is activated by green light and gene rates toxic radical species in tumors. We hypothesized that interstitial hy pericin and laser phototherapy would decrease pancreatic cancer growth. Methods. MiaPaCa-2 and PANG-1 cells were grown in tissue culture. In vitro experiments were performed with addition of 10 mu g of hypericin/500,000 ca ncer cells, Cells were incubated with hypericin for 2 h. Cells mere then ex posed to KTP532 green laser light for 1 min at 0.6 W using a cylindrical di ffuser tip. Cell growth was measured by MTT assay 24 h after laser treatmen t, N = 12, MiaPaCa-2 cells were implanted subcutaneously and orthotopically in pancreas of nude mice. After 5 weeks, both tumors were injected with 10 0 mu g Of hypericin followed by insertion of a cylindrical diffuser tip int o the tumor center. Mice received 200J KTP laser light at 1.0 W in two site s. 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 suppresse d by 66.1 +/- 0.2%, n = 12, P < 0,01, ANOVA, Subcutaneous shoulder tumors w ere suppressed by 91.2 +/- 2.3%, n = 12, P < 0.001, and orthotopically grow n pancreatic tumors were suppressed by 42.2 +/- 8.1%, n = 12, P < 0.05, com pared to pretreatment sizes. Data expressed as percentage reduction vs pair ed controls in the MTT assay and vs pre-photodynamic therapy in mice experi ments. Paired Student's t tests were performed vs pretreatment sizes. Conclusion. Both in vitro and in, vivo results revealed a significant decre ase in pancreatic cancer cell growth. Laser or dye alone had no effect, ind icating that intratumor hypericin and laser therapy may prove useful in unr esectable pancreatic cancer. (C) 2000 Academic Press.