Evaluation of doxorubicin in three-dimensional culture of breast cancer cells and the response in PI3K/AKT/PTEN signaling pathways: a pilot study

Evaluation of doxorubicin in three-dimensional culture of breast cancer cells and the response in PI3K/AKT/PTEN signaling pathways: a pilot study

Breast cancer (BC) has a high mortality rate, which is attributed to the absence of effective treatment markers. Doxorubicin (DOX) was evaluated by molecular docking in vitro in cultured BC spheroids and its association with genes involved in the PI3K/AKT/PTEN signaling pathway. Spheroids were obtai...

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Published in:Women & health Vol. 62; no. 6; pp. 467 - 475
Main Authors: Gobbo, Marina Guimarães, de Mendonça Fernandes, Gláucia Maria, Fernandes-Ferreira, Rafael, Caires, Lennon Pereira, Caldas, Heloisa Cristina, de Campos Zuccari, Débora Aparecida Pires, Bordin-Junior, Newton Antonio, Gonçalves Vidotti, Giovana Aparecida, Souza, Doroteia Rossi Silva
Format: Journal Article
Language:English
Published: United States Taylor & Francis 03-07-2022
Taylor & Francis LLC
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Angiogenesis
Breast cancer
Cancer
Cell culture
Cell proliferation
Chemotherapy
Doxorubicin
Gene expression
Genes
Hypoxia-inducible factor 1a
Kinases
Molecular docking
Molecular modelling
Pilot projects
PTEN protein
Signal transduction
Spheroids
three-dimensional culture
Tumors
Vascular endothelial growth factor
three-dimensional culture
chemotherapy
Breast cancer
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Summary:Breast cancer (BC) has a high mortality rate, which is attributed to the absence of effective treatment markers. Doxorubicin (DOX) was evaluated by molecular docking in vitro in cultured BC spheroids and its association with genes involved in the PI3K/AKT/PTEN signaling pathway. Spheroids were obtained from a primary BC. The selected compound was used for molecular docking experiments. Spheroids were treated with DOX for 1 (D1) and 9 (D9) days. qPCR was used to evaluate PIK3CA, HIF-1α, VEGF-A, PTEN expression. Treatment with DOX (1 µM) significantly increased the number of spheroids (D1), whereas exposure to chemotherapy at 2 µM on D9 was more effective. DOX treatment resulted in significantly higher expression of VEGF-A, HIF-1α and PIK3CA by D1 and HIF-1α and PTEN were upregulated by D9. Compared to treatment on D1 with D9 (1 μM) had significantly higher PTEN and lower PIK3CA gene expression. The genes HIF-1α and PTEN were more expressed with 2 μM of DOX while VEGF-A was downregulated. D1 vs. D9 exhibited reduced VEGF-A, HIF-1α, and PIK3CA expression and upregulation of PTEN expression. DOX effects at the molecular mechanisms can be involved the modulation of genes related to angiogenesis cell proliferation and tumor growth in BC tissue spheroids.
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ISSN:0363-0242
1541-0331
DOI:10.1080/03630242.2022.2085842