Related Experiment Video

Updated: Sep 29, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.4K

CDK Inhibition Reverses Acquired 5-Fluorouracil Resistance in Hepatocellular Carcinoma Cells

Yiyi Pu1,2, Dongmei Yan2, Linglan Tu2

  • 1Department of the Hepato-Biliary-Pancreatic Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.

Disease Markers
|March 21, 2022
PubMed
Abstract

Insights

This study reveals that inhibiting cell cycle-dependent kinases (CDKs) can overcome 5-Fluorouracil (5-FU) resistance in hepatocellular carcinoma (HCC) cells, offering new therapeutic strategies for liver cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • 5-Fluorouracil (5-FU) is a key chemotherapy agent, but its efficacy in hepatocellular carcinoma (HCC) is hampered by acquired resistance.
  • Identifying molecular targets is crucial to enhance 5-FU sensitivity in HCC treatment.

Purpose of the Study:

  • To identify proteins involved in 5-FU resistance in HCC.
  • To investigate the role of these proteins in modulating 5-FU sensitivity in HCC cells.

Main Methods:

  • Mass spectrometry (MS) proteomics was employed to compare protein expression between 5-FU-resistant (BEL7402/5-FU) and parental (BEL7402) HCC cell lines.
  • Bioinformatics tools were used to identify differentially expressed proteins and select key hub proteins.
  • Cell Counting Kit 8 (CCK8) assays were performed to assess the effect of CDK inhibitors on 5-FU sensitivity.

Main Results:

  • Proteomic analysis identified differentially expressed proteins between the resistant and parental cell lines.
  • Cell cycle-related kinases (CDKs) were identified as potential targets modulating 5-FU resistance.
  • Inhibition of CDKs significantly reduced the IC50 of 5-FU in resistant HCC cells, as confirmed by CCK8 assays.

Conclusions:

  • CDK inhibition effectively reverses acquired 5-FU resistance in HCC cells.
  • Targeting CDKs presents a promising strategy to improve the therapeutic outcomes of 5-FU chemotherapy in liver cancer.

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.0K
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

Related Concept Videos

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...
5.0K
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
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
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