Related Experiment Video

Updated: Dec 28, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

2.0K

MTH1 Inhibitor TH287 Suppresses Gastric Cancer Development Through the Regulation of PI3K/AKT Signaling

Dankai Zhan1, Xinxin Zhang1, Jiahui Li2

  • 1Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Cancer Biotherapy & Radiopharmaceuticals
|February 21, 2020
PubMed

Insights

The MTH1 inhibitor TH287 shows promise as an anticancer agent for gastric cancer. It effectively reduces tumor cell viability, migration, and proliferation by impacting mitochondrial function and PI3K/AKT signaling.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • MutT homologue-1 (MTH1) is crucial for cancer cell survival by mitigating oxidative stress and maintaining genome integrity.
  • MTH1 inhibitors are emerging as potential anticancer therapeutics, but their precise mechanisms require further elucidation.
  • Gastric cancer (GCa) remains a significant health concern, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the anticancer effects of the MTH1 inhibitor TH287 on gastric cancer cells.
  • To characterize the underlying mechanisms of TH287's action, focusing on cell viability, migration, apoptosis, cell cycle, and signaling pathways.

Main Methods:

  • Gastric cancer cell lines (BGC-823, SGC-7901) were treated with TH287.
  • Assays included CCK-8 for viability, colony-forming for proliferation, Transwell and scratch assays for migration, and flow cytometry for apoptosis and cell cycle analysis.
  • Mitochondrial membrane potential (JC-1 staining) and protein expression (Western blotting for PI3K/AKT pathway) were assessed.

Main Results:

  • TH287 significantly inhibited gastric cancer cell viability, proliferation, and migration.
  • The compound induced apoptosis and G2/M cell cycle arrest.
  • TH287 treatment led to loss of mitochondrial membrane potential and altered Bcl-2/Bax expression.
  • These effects were linked to the inhibition of the pro-oncogenic PI3K/AKT signaling pathway.

Conclusions:

  • TH287 exhibits potent anticancer effects against gastric cancer cells.
  • The drug's efficacy is mediated by disruption of mitochondrial function and suppression of PI3K/AKT signaling.
  • TH287 represents a promising novel therapeutic candidate for gastric cancer treatment.
Keywords:
MuT homologue-1TH287gastric cancer

More Related Videos

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.7K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.5K

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...
4.5K
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...
5.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.6K
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...
5.5K
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...
5.0K
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...
7.6K