Related Experiment Video

Updated: Sep 27, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

Rapamycin induces Smad activity in prostate cancer cell lines

H G van der Poel1, C Hanrahan, H Zhong

  • 1Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Department of Urology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. h_vanderpoel@hotmail.com

Urological Research
|February 25, 2003
PubMed

Insights

Rapamycin inhibits prostate cancer cell growth by affecting gene expression and activating TGF-beta/BMP signaling. Combining rapamycin with PI3K inhibitors enhances its anticancer effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Rapamycin targets the FKBP12/mTOR complex, inhibiting cell cycle progression.
  • The exact mechanisms of rapamycin's growth inhibition, particularly in prostate cancer, require further elucidation.
  • Prostate cancer cell lines LNCaP and PC3 exhibit sensitivity to rapamycin.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying rapamycin's growth inhibitory effects in human prostate cancer cells.
  • To identify specific genes regulated by rapamycin in LNCaP and PC3 cells.
  • To explore the role of TGF-beta/BMP signaling and the potential of combining rapamycin with PI3K inhibition.

Main Methods:

  • Treatment of LNCaP and PC3 cells with rapamycin and LY294002 (PI3K inhibitor).
  • Assessment of cell growth inhibition and determination of inhibitory doses (ID50).
  • Filter cDNA array analysis to identify gene expression changes.
  • Western blotting and Smad-reporter assay to evaluate TGF-beta/BMP signaling pathway activation.

Main Results:

  • Rapamycin inhibited growth in LNCaP (ID50: 93 nM) and PC3 (ID50: 50 nM) cells.
  • Rapamycin altered the expression of key genes, including down-regulation of follistatin and eukaryotic initiation factor-4E (eIF4E), and up-regulation of bone morphogenetic protein (BMP)-4.
  • Rapamycin induced BMP4, reduced follistatin, promoted nuclear Smad4 expression, and activated TGF-beta/BMP signaling, which was further enhanced by PI3K inhibition.

Conclusions:

  • Smad signaling is implicated in the anticancer activity of rapamycin.
  • Combination therapy with rapamycin and PI3K inhibitors potentiates growth inhibition in prostate cancer cells.
  • Understanding these molecular pathways provides a basis for developing novel therapeutic strategies for prostate cancer.

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration06:21

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration

Published on: April 27, 2018

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...