title: Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell.
abstract: OBJECTIVE
  Resistance to chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic carcinoma. Myeloid cell leukemia-1 (Mcl-1) is highly up-regulated in pancreatic carcinoma and is associated with the anti-apoptosis and the resistance to chemotherapy drugs. Suppression of Mcl-1 would be an approach to induce apoptosis and enhance the chemosensitivity.
  
  
  METHODS
  In this study, three pancreatic cancer cell lines (PANC-1, BxPC-3 and SW1900) stably expressing shRNAs targeting Mcl-1 gene were established and gene expression inhibition was assessed by Real-Time QPCR and Western blotting. The effects of Mcl-1 downregulation mediated by RNAi were explored in vitro and in vivo.
  
  
  RESULTS
  We showed that the specific downregulation of Mcl-1 strikingly inhibited cell growth, colony formation, cell cycle arrest and induced apoptosis in pancreatic cancer cells in vitro, and markedly decreased the tumorigenicity in a mouse xenograft model. Moreover, knockdown of Mcl-1 significantly increased the chemosensitivity to Gemcitabine in pancreatic carcinoma cells.
  
  
  CONCLUSIONS
  Our data suggests that the specific downregulation of Mcl-1 by RNAi is a promising approach to induce apoptosis and enhance the chemosensitivity for pancreatic carcinoma gene therapy.
authors.affiliation: Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038, Xi'an, Shaanxi, China.
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Wei
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Shen
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D055029:Inverted Repeat Sequences; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D000093542:Gemcitabine