title: Synergistic effects of photodynamic therapy with HPPH and gemcitabine in pancreatic cancer cell lines.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) is a potential treatment for pancreatic cancer. A second-generation photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide (HPPH) has a long wavelength absorption, high-tumor selectivity, and shorter duration of skin photosensitivity. We investigated the efficacy of PDT with HPPH and gemcitabine in inducing cell death in multiple pancreatic cancer cell lines.
  
  
  METHODS
  We used three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BXPC-3) incubated with HPPH concentration of 0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, and 0.5 µg/ml for 6 hours, followed by photoradiation at a light dose of 60 J/cm(2). Afterwards, each cell line was treated with gemcitabine at concentrations of 0, 1, 10, and 100 µM and incubated for another 96 hours. Cell death was detected with SYTOX green staining. We also assessed the difference in cytotoxicity in adding gemcitabine before and after PDT.
  
  
  RESULTS
  HPPH-PDT can effectively induce cell death in all cell lines in a dose-dependent manner, with a 100% of cell death at the 0.5 µg/ml HPPH concentration. In contrast, monotherapy with gemcitabine alone (100 µM) only achieved <45% cell death. Combining gemcitabine to HPPH-PDT resulted in synergistic cytotoxic effect with 20-50% more cell death across all cell lines. There was no difference in cytotoxicity in adding gemcitabine before or after PDT.
  
  
  CONCLUSIONS
  This is the first study on HPPH-PDT for pancreatic cancer. HPPH-PDT-induced cell death occurs in a dose-dependent manner. HPPH-PDT and gemcitabine have synergistic effects in inducing cell death in multiple pancreatic cancer cell lines.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.forename: Marlys A
authors.initials: MA
authors.lastname: Anderson
authors.forename: Emmanuel C
authors.initials: EC
authors.lastname: Gorospe
authors.forename: Cadman L
authors.initials: CL
authors.lastname: Leggett
authors.forename: Lori S
authors.initials: LS
authors.lastname: Lutzke
authors.forename: Louis M
authors.initials: LM
authors.lastname: Wong Kee Song
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D017319:Photosensitizing Agents; D003841:Deoxycytidine; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D000093542:Gemcitabine