The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation

Biochem Biophys Res Commun. 2005 May 27;331(1):295-302. doi: 10.1016/j.bbrc.2005.03.166.


We present immunohistochemical evidence that the mTOR/p70s6k pathway is activated in pancreatic tumors and show that the mTOR inhibitor and rapamycin analog CCI-779 potently suppresses the proliferation of pancreatic cancer cells. Consistent with a recent study, CCI-779 increased c-Jun phosphorylation (Ser63) in a dose- and time-dependent manner, and induced apoptosis in p53-defective BxPC-3 cells. In contrast to the study, however, we observed that CCI-779 concomitantly increased c-Jun protein levels and that its ability to induce apoptosis might not require the activated c-Jun. Furthermore, CCI-779 neither induced c-Jun phosphorylation in other p53-defective pancreatic cancer cells (MiaPaCa-2) nor inhibited their proliferation. c-Jun, in fact, appeared to be partly responsible for the resistance of MiaPaCa-2 cells to CCI-779. Together, these results indicate a complex role for c-Jun in cellular responses to CCI-779 and provide an important basis for investigating CCI-779 further as a potential therapeutic agent for pancreatic tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Immunohistochemistry
  • Mutation
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phosphorylation
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / genetics
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use*
  • TOR Serine-Threonine Kinases
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-jun
  • temsirolimus
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus