The Interaction of PI3K Inhibition with Homologous Recombination Repair in Triple Negative Breast Cancer Cells
| Autor: | Gamze Guney Eskiler |
|---|---|
| Přispěvatelé: | Eskiler, GG, Sakarya Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri Bölümü, Güney Eskiler, Gamze |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA damage Morpholines RAD51 Pharmaceutical Science lcsh:RS1-441 Antineoplastic Agents Apoptosis Triple Negative Breast Neoplasms lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases Structure-Activity Relationship 0302 clinical medicine Downregulation and upregulation Annexin Tumor Cells Cultured Medicine Humans LY294002 Pharmacology & Pharmacy Enzyme Inhibitors PI3K/AKT/mTOR pathway Triple-negative breast cancer Cell Proliferation Pharmacology Dose-Response Relationship Drug Kinase business.industry lcsh:RM1-950 Recombinational DNA Repair 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry Chromones Cancer research Drug Screening Assays Antitumor business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Pharmacy & Pharmaceutical Sciences, Vol 22, Iss 1 (2019) |
| ISSN: | 1482-1826 |
| Popis: | Purpose: Aberrant activation of the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway is observed in many types of human cancer including triple negative breast cancer (TNBC). Additionally, dysregulation in the homologous recombination (HR)-dependent DNA-repair is associated with TNBC phenotype due to BRCA1/2 mutations or HR deficiency. Therefore, the hypothesis of this study was to evaluate the association of PI3K inhibition with HR pathway in TNBC in terms of BRCA1 mutation status. Methods: To examine the potential therapeutic effect of LY294002, an inhibitor of PI3K, on TNBC cell lines with known BRCA1 status, WST-1, annexin V, cell cycle analysis and AO/EB staining were performed. Additionally, RT-PCR and immunofluorescence analysis was used to explore the interaction between the inhibition of PI3K and HR functionality. Results: The findings showed that LY294002 could significantly inhibited the proliferation of TNBC cells. Furthermore, the suppression of PI3K resulted in HR impairment by BRCA1 and RAD51 downregulation and apoptotic cell death by the induction of DNA damage and BAX overexpression. Therefore, LY294002 was more effective in BRCA1-deficient TNBC cells. Conclusions: Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with TNBC. |
| Databáze: | OpenAIRE |
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