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Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jul 05; Vol. 25 (13). Date of Electronic Publication: 2024 Jul 05. - Publication Year :
- 2024
-
Abstract
- Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.
- Subjects :
- Humans
Animals
Mice
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols pharmacology
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Female
Cyclin-Dependent Kinase 4 antagonists & inhibitors
Cyclin-Dependent Kinase 4 metabolism
Cell Proliferation drug effects
Mice, Nude
Cyclin-Dependent Kinase 6 antagonists & inhibitors
Cyclin-Dependent Kinase 6 metabolism
MCF-7 Cells
HCT116 Cells
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Antineoplastic Agents administration & dosage
Mice, Inbred BALB C
Benzimidazoles pharmacology
Benzimidazoles administration & dosage
Aminopyridines pharmacology
Aminopyridines administration & dosage
Drug Synergism
Xenograft Model Antitumor Assays
Desipramine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39000513
- Full Text :
- https://doi.org/10.3390/ijms25137407