Related Experiment Video

Updated: Mar 13, 2026

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

20.2K

Desmoplasia suppression by metformin-mediated AMPK activation inhibits pancreatic cancer progression

Wanxing Duan1, Ke Chen1, Zhengdong Jiang1

  • 1Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

Cancer Letters
|October 30, 2016
PubMed

Insights

Metformin, an AMP-activated protein kinase (AMPK) activator, may treat pancreatic cancer by reducing its dense stromal reaction. This study shows metformin inhibits tumor growth and enhances chemotherapy effects in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a dense stromal reaction.
  • AMP-activated protein kinase (AMPK) is a cellular energy sensor.
  • Metformin, an AMPK activator, shows potential in cancer therapy, but its effect on PDAC stroma is unknown.

Purpose of the Study:

  • To investigate the role of AMPK in PDAC and the effect of metformin on PDAC stromal reaction.
  • To evaluate metformin's efficacy in preclinical PDAC models.

Main Methods:

  • Assessed AMPK and phosphorylated-AMPK (P-AMPK) expression in normal and PDAC tissues.
  • Evaluated metformin's effects on pancreatic cancer cells (PCs) and pancreatic stellate cells (PSCs) in vitro and in a xenograft mouse model.
  • Investigated metformin's impact on fibrogenic cytokine production and PSC activation.

Main Results:

  • Reduced P-AMPK expression is frequent in PDAC, correlating with poor prognosis and dense stroma.
  • Metformin decreased fibrogenic cytokine production by PCs and inhibited PSC activation.
  • In vivo, metformin suppressed desmoplastic reaction, inhibited tumor growth, and enhanced gemcitabine efficacy.

Conclusions:

  • Reduced P-AMPK expression is linked to poor prognosis in PDAC.
  • Metformin, by activating AMPK, reduces the desmoplastic reaction in PDAC.
  • Metformin represents a potential therapeutic strategy for advanced PDAC, particularly when combined with chemotherapy.
Keywords:
AMP-activated protein kinase (AMPK)Desmoplastic reactionMetforminPancreatic cancerPancreatic stellate cells (PSCs)

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.4K
Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture08:16

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

Published on: February 11, 2019

9.4K

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...
5.0K
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...
6.1K
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
793
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...
6.1K
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