Related Experiment Video

Updated: Jun 18, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Regulation of prostate cancer cell proliferation by somatostatin receptor activation

Massimiliano Ruscica1, Marica Arvigo, Federico Gatto

  • 1Department of Endocrinology, Pathophysiology and Applied Biology, Università degli Studi di Milano, via G. Balzaretti 9, 20133 Milano, Italy.

Molecular and Cellular Endocrinology
|November 26, 2009
PubMed

Insights

New somatostatin (SRIF) agonists show promise in inhibiting prostate cancer (PCa) cell proliferation by targeting specific SRIF receptors (sst) and influencing the IGF system, offering potential new therapeutic strategies for PCa.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Somatostatin (SRIF) and its agonists have shown potential antitumoral effects, but data in prostate cancer (PCa) are limited and conflicting.
  • Prostate cancer (PCa) remains a significant health concern, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the effects of lanreotide and novel SRIF agonists on PCa cell proliferation and the IGF system in LNCaP cells.
  • To explore the role of somatostatin receptor (sst) dimerization in mediating these effects.

Main Methods:

  • Utilized LNCaP cells, a model of androgen-dependent PCa, to assess proliferation, receptor expression, and dimerization.
  • Treated cells with various SRIF agonists (lanreotide, BIM-23704, BIM-23244, BIM-23120, BIM-23206, BIM-23926) and an sst(2) antagonist (BIM-23627).
  • Analyzed changes in cell cycle regulators (p27Kip1, p21, cyclin E) and Insulin-like Growth Factor (IGF) system components (IGF-I, IGF-II, IGFBP-3).

Main Results:

  • LNCaP cells express sst(1), sst(2), sst(3), sst(5), with sst(1) and sst(3) inversely regulated by serum.
  • Constitutive sst(1)/sst(2) and sst(2)/sst(5) dimers were stabilized by specific agonists.
  • Lanreotide and BIM-23244 demonstrated potent inhibition of LNCaP cell proliferation, with sst(1) activation also showing significant antiproliferative effects.
  • SRIF agonists reduced IGF-I and IGF-II secretion, increased p27Kip1 and p21, decreased cyclin E, and reduced IGFBP-3 proteolysis.
  • Exogenous IGF-I, but not IGF-II, counteracted the antiproliferative effects.

Conclusions:

  • Activation of sst(1) and sst(2)/sst(5) receptors in LNCaP cells leads to significant antiproliferative and antisecretive actions.
  • SRIF agonists modulate the IGF system and cell cycle regulators, contributing to their anti-PCa effects.
  • Novel SRIF agonists, particularly those targeting sst(1) and sst(2)/sst(5) dimers, represent promising therapeutic candidates for prostate cancer.

More Related Videos

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

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...
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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...