Related Experiment Video

Updated: Sep 24, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.4K

Inducing Synergistic DNA Damage by TRIP13 and PARP1 Inhibitors Provides a Potential Treatment for Hepatocellular

Haojun Xu1, Zhijie Ma1, Xiao Mo2,1

  • 1School of Basic Medical Sciences &Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing 211166, China.

Journal of Cancer
|May 6, 2022
PubMed

Insights

Thyroid hormone receptor interactor 13 (TRIP13) inhibition impairs DNA repair in hepatocellular carcinoma (HCC). Combining TRIP13 inhibition with PARP1 inhibitors shows synergistic anti-cancer effects, offering a potential new HCC treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Thyroid hormone receptor interactor 13 (TRIP13) is implicated in various cancers.
  • Understanding TRIP13's role in hepatocellular carcinoma (HCC) is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the function of TRIP13 in HCC.
  • To explore the synergistic effects of TRIP13 and PARP1 inhibitors in HCC treatment.

Main Methods:

  • Cell proliferation and migration assays (CCK-8, Transwell).
  • TRIP13 knockdown using siRNA or lentivirus for in vitro and in vivo studies.
  • DNA damage assessment via H2AX phosphorylation.
  • Combination therapy with TRIP13 inhibitor (DCZ0415) and PARP1 inhibitor (Olaparib).

Main Results:

  • TRIP13 inhibition and DCZ0415 treatment increased H2AX phosphorylation, indicating DNA damage.
  • Combined DCZ0415 and Olaparib demonstrated synergistic anti-HCC activity.
  • TRIP13 overexpression correlated with early HCC recurrence and poorer survival.
  • SP1 transcription factor regulates TRIP13 up-regulation in HCC.

Conclusions:

  • DCZ0415 targeting TRIP13 inhibits HCC progression by impairing non-homologous end-joining repair.
  • Combination therapy with Olaparib offers a promising strategy for HCC treatment.
  • TRIP13 is a potential biomarker for HCC recurrence and survival.
Keywords:
DCZ0415H2AXPARP1TRIP13hepatocellular carcinoma

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.0K
Evaluating In Vitro DNA Damage Using Comet Assay10:43

Evaluating In Vitro DNA Damage Using Comet Assay

Published on: October 11, 2017

38.2K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K
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...
7.9K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.4K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.7K