Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma

Related Experiment Video

Updated: Jul 1, 2025

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
07:20

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Published on: May 28, 2014

14.0K

Borui Zhao1, Xuan Qin2, Rui Fu1

  • 1School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin 300070, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 13, 2024
PubMed

Insights

Researchers identified BCL2 associated athanogene-1 (BAG1) as a key driver of cisplatin resistance in oral squamous cell carcinoma (OSCC). Silencing BAG1 and using a CDK4/6 inhibitor with cisplatin shows promise for treating advanced OSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cisplatin resistance is a major obstacle in treating advanced oral squamous cell carcinoma (OSCC).
  • Biomarkers and mechanisms underlying cisplatin resistance in OSCC are not fully understood.
  • Head and neck squamous cell carcinoma (HNSCC) often exhibits elevated BCL2 associated athanogene-1 (BAG1) expression.

Purpose of the Study:

  • To investigate the role of BAG1 in cisplatin resistance in OSCC.
  • To explore therapeutic strategies targeting the CDK4/6-BAG1 axis for overcoming chemoresistance.
  • To develop a novel nanodrug delivery system for enhanced synergistic antitumor effects.

Main Methods:

  • Bioinformatic analysis to identify potential biomarkers.
  • BAG1 expression analysis in human OSCC tissues and cell lines.
  • In vitro and in vivo experiments involving BAG1 silencing and CDK4/6 inhibitor treatment.
  • Development and validation of a supramolecular nanodrug (LEE011-FFERGD/CDDP).

Main Results:

  • BAG1 was identified as a potential biomarker for cisplatin resistance in OSCC.
  • Silencing BAG1 induced apoptosis and reduced viability in cisplatin-resistant OSCC cells.
  • A positive correlation between BAG1 expression and G1/S cell cycle transition was observed.
  • Combined administration of a CDK4/6 inhibitor and cisplatin effectively overcame chemoresistance via the CDK4/6-BAG1 axis.
  • The novel nanodrug LEE011-FFERGD/CDDP demonstrated synergistic antitumor efficacy in an OSCC mouse model.

Conclusions:

  • BAG1 plays a crucial role in cisplatin resistance in OSCC.
  • Targeting the CDK4/6-BAG1 axis offers a potential therapeutic strategy for chemoresistant OSCC.
  • Combined therapy with CDK4/6 inhibitors and cisplatin, potentially delivered via novel nanodrugs, shows promise for advanced and cisplatin-resistant OSCC treatment.
Keywords:
BCL2-associated athanogene-1 (BAG1)CDK4/6 inhibitionCisplatin resistanceOSCCSupramolecular nanodrug

More Related Videos

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice08:57

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice

Published on: October 5, 2017

10.9K
Retroductal Nanoparticle Injection to the Murine Submandibular Gland07:45

Retroductal Nanoparticle Injection to the Murine Submandibular Gland

Published on: May 3, 2018

10.1K

Related Concept Videos

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...
7.6K
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...
4.7K
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...
3.3K