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Cited by 15PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesCancer, Lipids, and Metabolism

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

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Wu, Hua-Tao, Li, Chun-Lan, Fang, Ze-Xuan, Chen, Wen-Jia, Lin, Wen-Ting, Liu, Jing·2022·Frontiers in Pharmacology
DOI 10.3389/fphar.2022.873131PMC PMC9062109
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Abstract

Triple-negative breast cancer (TNBC) is the aggressive molecular type of breast carcinoma, with a high metastasis/relapse incidence and cancer-related death rate, due to lack of specific therapeutic targets in the clinic. Exploring potential therapeutic targets or developing novel therapeutic strategies are the focus of intense research to improve the survival and life quality of patients with TNBC. The current study focused on drugs targeting the mTOR signaling pathway by investigating the potential utilization of itraconazole (ITZ) combined with rapamycin in the treatment of TNBC. CCK-8, colony formation and transwell assays were conducted to evaluate the effect of ITZ with rapamycin in combination on MDA-MB-231 and BT-549 TNBC cells. Synergistic inhibition was found in terms of proliferation and motility of TNBC cells. However, apoptosis was not enhanced by the combined treatment of ITZ and rapamycin. Flow cytometry analysis showed that ITZ and/or rapamycin arrested cells in G0/G1 phase and prevented G1/S phase transition. Reduced cyclin D1 protein levels were consistent with G0/G1 phase arrest, especially when resulting from the combination of ITZ with rapamycin. In conclusion, the combination of ITZ with rapamycin is a promising therapeutic strategy for patients with TNBC through synergistically arresting cells in the G0/G1 phase of the cell cycle, rather than inducing apoptosis.

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Cited by

Sorted by citations

Authors
Wu, H.-T., Li, C.-L., Fang, Z.-X., Chen, W.-J., Lin, W.-T., & Liu, J.
Affiliations
  • Cancer Hospital of Shantou University Medical College (CN)
  • Shantou University (CN)
Corresponding author
Liu, Jing
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2022-04-19
Volume
13
Pages
873131-873131
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2022.873131
PMC
PMC9062109
OpenAlex
W4224215458
Cited by
15
References
2
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 1
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81501539)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
triple-negative breast cancer, itraconazole, rapamycin, mTOR signaling, cell cycle arrest, G0/G1 phase arrest, cyclin D1, combination therapy, synergistic inhibition, cell proliferation, cell motility, apoptosis

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