Related Experiment Video

Updated: Sep 5, 2025

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.8K

Enhancement of MDM2 inhibitory effects through blocking nuclear export mechanisms in ovarian cancer cells

Amal Alzahrani1, Umamaheswari Natarajan2, Appu Rathinavelu3

  • 1Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321, College Ave, Fort Lauderdale, Florida 33314, United States; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida, United States.

Cancer Genetics
|July 5, 2022
PubMed

Insights

Combining RG-7388 and Selinexor effectively treats ovarian cancer by reactivating p53 and inducing apoptosis. This combination therapy reduces cell viability and up-regulates tumor suppressor proteins.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Over 90% of ovarian cancers have p53 mutations or inactivation.
  • Exportin-1 (XPO1) overexpression, linked to chemotherapy resistance, exports p53 and tumor suppressors from the nucleus.
  • MDM2 inhibitor RG-7388 reactivates p53; Selinexor (a SINE inhibitor) increases nuclear p53 accumulation.

Purpose of the Study:

  • To evaluate the efficacy of combining RG-7388 and Selinexor for ovarian cancer treatment.
  • To investigate the molecular mechanisms underlying the combination therapy's effects.

Main Methods:

  • Ovarian cancer cell lines were treated with RG-7388, Selinexor, or a combination.
  • Cell viability assays were performed.
  • Western blotting was used to assess protein levels in whole lysate, cytoplasm, and nucleus, focusing on p53, p21, and other cancer suppressors.
  • Caspase activity was measured to confirm apoptosis induction.

Main Results:

  • The combination of Selinexor and RG-7388 significantly reduced ovarian cancer cell viability compared to individual treatments.
  • Combination therapy led to the up-regulation of multiple cancer suppressor proteins in all cellular compartments (lysate, cytoplasm, nucleus).
  • The treatment induced a caspase-mediated apoptotic pathway, evidenced by increased p53 and p21 expression.

Conclusions:

  • Combination therapy with Selinexor and RG-7388 is a promising strategy for ovarian cancer.
  • The synergistic effect involves p53 reactivation, increased nuclear retention of tumor suppressors, and induction of apoptosis.
  • This approach warrants further investigation for clinical application in ovarian cancer patients.
Keywords:
ApoptosisRG-7388Selinexorp21p53

More Related Videos

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

6.8K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.4K

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...
4.6K
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...
4.9K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.1K
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...
2.1K
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...
2.0K
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...
6.6K