title: Combined colonic cancer treatment with vitamin D analogs and irinotecan or oxaliplatin.
abstract: aim: The aim of this study was the evaluation of the antitumor effect of two synthetic analogs of vitamin D, PRI-2191 and PRI-2205 in combined treatment with irinotecan or oxaliplatin on mouse (MC38) and human (HT-29) colon cancer cells.
  
  
  METHODS
  Mice bearing subcutaneous tumors were injected with vitamin D analogs and with irinotecan or oxaliplatin, according to various schedules.
  
  
  RESULTS
  Statistically significant inhibition of MC38 tumor growth by combined therapy was observed. When analogs were used in combined treatment with irinotecan, survival times of mice were significantly prolonged. We also observed improved antitumor effects in combined treatment with oxaliplatin in mice bearing HT-29 tumors, however, antagonism in life span prolongation was observed. Analog PRI-2191 increased the expression of vitamin D receptor (VDR), retinoic X receptor-α (RXRα) and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) in HT-29 tumors when used alone. VDR and RXRα expressions were up-regulated by PRI-2191 analog, as compared to oxaliplatin alone.
  
  
  CONCLUSIONS
  The obtained results suggest that vitamin D analogs could be used in combined colonic cancer treatment with irinotecan or oxaliplatin. However, the regulation of ERK1/2 expression by both analogs and oxaliplatin may explain the observed antagonistic interactions.
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla St, 12, 53-114, Wroclaw, Poland.
authors: Magdalena
authors: M
authors: Milczarek
authors: Sara
authors: S
authors: Rosinska
authors: Mateusz
authors: M
authors: Psurski
authors: Magdalena
authors: M
authors: Maciejewska
authors: Andrzej
authors: A
authors: Kutner
authors: Joanna
authors: J
authors: Wietrzyk
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage; D005260:Female; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D015398:Signal Transduction / Q000187:drug effects; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004100:Dihydroxycholecalciferols; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D014807:Vitamin D; C023850:1 alpha,24-dihydroxyvitamin D3; D000077146:Irinotecan; D002166:Camptothecin