Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in

Related Experiment Video

Updated: Apr 13, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

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

18.9K

Ira K Gordon1, Jie Lu2, Christian A Graves1

  • 1Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Molecular Cancer Therapeutics
|May 6, 2015
PubMed

Insights

Inhibiting protein phosphatase 2A (PP2A) with LB100 enhances glioblastoma cell sensitivity to radiation therapy. This combination therapy reduces tumor growth and improves survival by impairing DNA repair and increasing cell death.

Area of Science:

  • Oncology
  • Cancer Biology
  • Radiotherapy

Background:

  • Protein phosphatase 2A (PP2A) is a tumor suppressor frequently inactivated in cancers.
  • Inhibiting PP2A is an emerging strategy to sensitize cancer cells to radiotherapy.
  • Glioblastoma is an aggressive brain tumor with limited treatment options.

Purpose of the Study:

  • To investigate the effects of PP2A inhibition using LB100 on U251 glioblastoma cells treated with radiotherapy.
  • To evaluate the efficacy of combination LB100 and radiotherapy in vitro and in a xenograft mouse model.
  • To elucidate the mechanisms underlying PP2A inhibition-induced radiosensitization.

Main Methods:

  • In vitro studies on U251 glioblastoma cells.
  • In vivo studies using a glioblastoma xenograft mouse model.
  • Assessed PP2A activity, γ-H2AX expression, mitotic catastrophe, and p53 expression.
  • Measured tumor growth delay and mouse survival.

Main Results:

  • LB100 treatment attenuated radiation-induced PP2A activity.
  • Combination therapy resulted in a radiation dose enhancement factor of 1.45.
  • Increased mitotic catastrophe and diminished DNA double-strand break repair (indicated by sustained γ-H2AX expression) were observed.
  • Combination treatment significantly delayed tumor growth, prolonged survival, and decreased p53 expression.

Conclusions:

  • LB100 effectively inhibits PP2A activity and enhances glioblastoma radiosensitivity.
  • Combination therapy with LB100 and radiation offers a promising strategy for glioblastoma treatment.
  • Radiosensitization is mediated by increased mitotic catastrophe, impaired DNA repair, and reduced p53 activity.

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.8K
In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology13:17

In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology

Published on: September 29, 2023

3.3K

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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.2K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.3K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
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