siRNA directed against survivin enhances pancreatic cancer cell gemcitabine chemosensitivity

Dig Dis Sci. 2009 Jan;54(1):89-96. doi: 10.1007/s10620-008-0329-4. Epub 2008 Jul 2.

Abstract

Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and to cause resistance to radiation and chemotherapy, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In our study, a short interfering RNA (siRNA) plasmid expression vector against survivin was constructed and transfected into human pancreatic cancer cell lines of Panc-1 and BxPC3. The expression of survivin mRNA and protein among the stable transfected cells and the untransfected cells was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. Tumor cell growth in vitro was assessed by trypan blue exclusion. The cell cycle distribution and cell apoptosis were measured by flow cytometry. The cytotoxicity assay was measured by the MTT test. Our results showed that survivin siRNA treatment caused a specific and profound decrease of survivin mRNA and protein that was associated with decreased cell growth, spontaneous apoptosis, and a specific G0/G1 arrest. Furthermore, the suppression of survivin can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine significantly. We suggest that the RNAi against survivin gene strategy would be a potential approach to chemosensitization therapy in human pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Plasmids / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • Survivin
  • Transfection

Substances

  • Antimetabolites, Antineoplastic
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Survivin
  • Deoxycytidine
  • gemcitabine