title: Anti-tumor effect of the extract from qingyihuaji formula on pancreatic cancer by down-regulating Notch-4 and Jagged-1.
abstract: OBJECTIVE
  To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription--Qingyi-huaji formula (QYHJ)--from Traditional Chinese Medicine (TCM).
  
  
  METHODS
  Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups: Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors (Notch-1, Notch-2, Notch-3, and Notch-4) and their Jagged ligands (Jagged-1 and Jagged-2) in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells (CSCs), to evaluate the impact of QYHJ extract on pancreatic CSCs.
  
  
  RESULTS
  QYHJ extract treatment effectively inhibited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups (P < 0.05), while gemcitabine alone had no significant effect in down-regulating Jagged-1 (P > 0.05). No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group (P > 0.05). Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment (P < 0.05), and the combined treatment was more effective than gemcitabine alone (P < 0.05).
  
  
  CONCLUSIONS
  The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xu
authors.forename: Feiye
authors.initials: F
authors.lastname: Zhu
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.forename: Luming
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D004365:Drugs, Chinese Herbal; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C550234:Qingyihuaji; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C073572:Notch4 protein, mouse