Related Experiment Video

Updated: Apr 14, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.9K

Mitogen-activated protein kinase inhibition reduces mucin 2 production and mucinous tumor growth

Ashok K Dilly1, Xinxin Song1, Herbert J Zeh1

  • 1Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Translational Research : the Journal of Laboratory and Clinical Medicine
|April 19, 2015
PubMed

Insights

Targeting the MAPK pathway with MEK inhibitors like RDEA119 effectively reduced mucin 2 (MUC2) production and pseudomyxoma peritonei (PMP) tumor growth, improving survival in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by excessive mucin 2 (MUC2) accumulation in the peritoneum.
  • The mitogen-activated protein kinase (MAPK) signaling pathway is upregulated in PMP and influences MUC2 production.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting the MAPK pathway to reduce MUC2 production and PMP tumor growth.
  • To evaluate the efficacy and safety of RDEA119, a MEK1/2 inhibitor, in preclinical PMP models.

Main Methods:

  • RDEA119 was tested in MUC2-secreting LS174T cells, human PMP explant tissue, and an intraperitoneal murine xenograft model.
  • Inhibition of ERK1/2 phosphorylation, MUC2 mRNA and protein expression, and downstream signaling pathways were assessed.

Main Results:

  • RDEA119 significantly reduced MUC2 production and ERK1/2 phosphorylation in vitro.
  • In vivo, RDEA119 treatment inhibited PMP tumor growth, downregulated phosphorylated ERK1/2 and nuclear factor κB p65 signaling, and reduced AP1 binding to the MUC2 promoter.
  • This led to a significant improvement in survival in the xenograft model.

Conclusions:

  • Targeted inhibition of the MAPK pathway using MEK inhibitors is a promising therapeutic strategy for PMP.
  • RDEA119 demonstrates preclinical efficacy in reducing MUC2 production and PMP tumor burden, supporting its potential use in PMP treatment.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.9K
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development11:02

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

21.9K

Related Concept Videos

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...
5.4K
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...
5.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.5K
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...
6.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K