Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy

Int J Mol Sci. 2012 Dec 21;14(1):273-85. doi: 10.3390/ijms14010273.

Abstract

Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Cadaverine / analogs & derivatives
  • Cadaverine / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Flow Cytometry
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • NIH 3T3 Cells
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / ultrastructure
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Vacuoles / drug effects
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • TOR Serine-Threonine Kinases
  • monodansylcadaverine
  • Cadaverine
  • Sirolimus