title: Calcitriol enhances the effect of photodynamic therapy in human breast cancer.
abstract: OBJECTIVE
  To investigate the killing effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on human breast cancer MCF7 and MDA-MB-231 cells in vitro.
  
  
  METHODS
  MCF7 and MDA-MB-231 breast cancer cells cultured in vitro were incubated with calcitriol (concentration of 10-8M, 10-10 M, 10-12 M, 10-14 M, 10-16 M, 0 M) to determine a proper concentration. The cells were divided into experimental group (calcitriol, HPD group and laser), HPD group (HPD and laser), calcitriol group (calcitriol and laser), blank laser group (laser alone) and blank group (no drugs and laser). Then the cells were preconditioned with calcitriol for 48 hrs and incubated with HPD for 6 hrs. After light exposure with 630 nm laser, the cells' viability and the reactive oxygen species (ROS) were assessed. After 8 hrs, flow cytometry was applied to detect the rate of cell apoptosis. The fluorescence intensity in cells was detected. Furthermore, the expression of porphyrin synthetic enzymes in pretreated breast cancer cells was analyzed.
  
  
  RESULTS
  MTT assay showed that the viability of cells in the experimental group was lowest (p<0.05). The ROS intensity of the experimental group was higher (p<0.01). The rate of cell apoptosis was higher in the experimental group (p<0.05), and the fluorescence of the experimental group was higher (p<0.01). Furthermore, mechanistic studies documented that the expression of the porphyrin synthesis enzyme coproporphyrinogen oxidase (CPOX) was increased by calcitriol at the mRNA level.
  
  
  CONCLUSIONS
  This research revealed a simple, non-toxic and highly effective preconditioning regimen to selectively enhance protoporphyrin IX (PpIX) fluorescence and the response of HPD-PDT in breast cancer search. This finding suggests that the combined treatment of breast cancer cells with calcitriol plus HPD may provide an effective and selective therapeutic modality to enhance HPD-induced PpIX fluorescent quality for improving discrimination of tumor tissue and PDT efficacy.
authors.affiliation: Cancer Center, Southern Medical University, Guangzhou, China.
authors.forename: Zhongzhong
authors.initials: Z
authors.lastname: Peng
authors.forename: Rengeng
authors.initials: R
authors.lastname: Liu
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Cai
authors.forename: Libo
authors.initials: L
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003304:Coproporphyrinogen Oxidase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003304:Coproporphyrinogen Oxidase; D002117:Calcitriol