The efficacy of tyrosine kinase inhibitors on human pancreatic cancer cell lines

Robert Saeid Farivar, James Gardner-Thorpe, Hiromichi Ito, Hassan Arshad, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang

Research output: Contribution to journalArticlepeer-review

Abstract

Background. We attempted to determine potential therapeutic targets in pancreatic cancer by performing microarray analysis and targeted chemotherapy on three human pancreatic cancer cell lines. Materials and methods. We used a microarray to screen 847 genes involved in cytokine signaling, signal transduction, and transcription. Tyrosine kinases represented a common target driving proliferation among the three cell types. We tested the ability of Gleevec (STI-571), Lavendustin, Herbimycin, and Genistein to inhibit the proliferation of cells in culture as assessed by the MTT assay. Results. Eighteen genes were found to be commonly expressed by the three cell lines. Of these, six (33%) included tyrosine phosphorylation signaling as part of the pathway. The most highly expressed common transcript was the EphB3 receptor, which is a tyrosine kinase. Herbimycin and Genistein were able to inhibit the proliferation of all three cell lines in a dose dependent manner, with a mean IC50 of 1.71 μM and 223 μM, respectively; whereas Lavendustin and Gleevec were ineffective in the inhibition of proliferation. Conclusions. Transcriptional profiling yielded common targets and insights into the biology of cells in culture. Herbimycin- and Genistein-based kinase inhibitors may offer potential and should be tested in other in vivo models for their ability to inhibit the growth of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalJournal of Surgical Research
Volume115
Issue number2
DOIs
StatePublished - Dec 2003

Keywords

  • Array
  • Cancer
  • Cell culture
  • Ephrin
  • Genistein
  • Herbimycin
  • Kinase inhibitor
  • Pancreas
  • Tyrosine kinase

ASJC Scopus subject areas

  • Surgery

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