title: PANC-1 pancreatic cancer cell growth inhibited by cucurmosin alone and in combination with an epidermal growth factor receptor-targeted drug.
abstract: OBJECTIVE
  To investigate the inhibition of PANC-1 pancreatic cancer cell growth by cucurmosin (CUS) and its possible mechanism.
  
  
  METHODS
  We observed the inhibition of PANC-1 cell growth by sulforhodamine B and colony-forming experiments in vitro and established nonobese diabetic/severe combined immunodeficiency mouse subcutaneous tumor models in vivo. We used Western blot to analyze protein levels related to apoptosis and epidermal growth factor receptor (EGFR) signaling pathways after drug intervention, whereas the messenger RNA expression of EGFR was analyzed by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  Sulforhodamine B and colony-forming experiments indicated that CUS inhibited PANC-1 cell proliferation in a dose- and time-dependent manner. A stronger inhibitory effect was observed when CUS was combined with gefitinib. The subcutaneous tumor growth was also inhibited. Western blot showed that all the examined proteins decreased, except for 4E-BP1 and the active fragments of caspase 3 and caspase 9 increased. Epidermal growth factor receptor expression did not change significantly in quantitative real-time polymerase chain reaction.
  
  
  CONCLUSIONS
  Cucurmosin can strongly inhibit the growth of PANC-1 cells in vitro and in vivo. Cucurmosin can down-regulate EGFR protein expression, but not at the messenger RNA level. Cucurmosin can also inhibit the ras/raf and phosphatidylinositol 3-kinase/Akt downstream signaling pathways and enhance the sensitivity of the EGFR-targeted drug gefitinib.
authors: From the *Union Clinical School, and †Department of Pharmacology, Fujian Medical University, Fuzhou, China; ‡Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou, China; and §State Structural Chemistry Key Laboratory of Fujian Institute of Research on Structure of Matter, Chinese Academy of Sciences, Fuzhou, China.
authors: Congfei
authors: C
authors: Wang
authors: Aiqin
authors: A
authors: Yang
authors: Baoming
authors: B
authors: Zhang
authors: Qiang
authors: Q
authors: Yin
authors: Heguang
authors: H
authors: Huang
authors: Minghuang
authors: M
authors: Chen
authors: Jieming
authors: J
authors: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010940:Plant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010940:Plant Proteins; D011799:Quinazolines; D054789:Ribosome Inactivating Proteins, Type 1; C412450:cucurmosin protein, Cucurbita moschata; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D000077156:Gefitinib