title: Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers.
abstract: BACKGROUND
  Photodynamic therapy (PDT) contains a photosensitizing process, which includes cellular uptake of photosensitizer and delivery of light to the target. ATP-binding cassette subfamily G2 (ABCG2) regulates endogenous protoporphyrin levels. In human colon cancers, it is not fully examined the role of ABCG2 in porphyrin-based photodynamic therapy.
  
  
  METHODS
  SW480 and HT29 cells were selected because they showed low and high ABCG2 expression levels, respectively. Pyropheophorbid-a (PPa) was used as a photosensitizer. Cells were exposed to a 670 nm diod laser. Cell viability and necrosi apoptosis was examined. Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system.
  
  
  RESULTS
  SW480 cells, which expressed lower level of ABCG2, showed the higher uptake of PPa than HT-29 cells. The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells. To confirm the ABCG2 effect on PDT, we established ABCG2 over-expressing stable cells in SW480 cells (SW480/ABCG2). Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells. The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.
  
  
  CONCLUSIONS
  ABCG2 plays an important role in determining the PDT efficacy by controlling the photosensitizer efflux rate. This implies the control of ABCG2 expression may be a potential solution to enhance photosensitivity.
authors.affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. jhsubzero@naver.com.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. parkjerry@catholic.ac.kr.|Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-071, South Korea. parkjerry@catholic.ac.kr.
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Park
authors.affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. shdbswls@naver.com.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Roh
authors.affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. iwkim@catholic.ac.kr.
authors.forename: In-Wook
authors.initials: IW
authors.lastname: Kim
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. thasan@mgh.harvard.edu.
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. choim@catholic.ac.kr.
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Choi
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054659:Diketopiperazines; D004195:Disease Models, Animal; D015870:Gene Expression; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C541506:3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester; C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D054659:Diketopiperazines; D006576:Heterocyclic Compounds, 4 or More Rings; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000241:Adenosine