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

Author(s)

Gobbo, Marina Guimaraes ; de Mendonca Fernandes, Glaucia Maria ; Fernandes-Ferreira, Rafael ; Caires, Lennon Pereira ; Caldas, Heloisa Cristina ; de Campos Zuccari, Debora Aparecida Pires ; Bordin-Junior, Newton Antonio ; Goncalves Vidotti, Giovana Aparecida ; Souza, Doroteia Rossi Silva

• Document type: Journal article
• Source: WOMEN & HEALTH; v. N/A, p. 9-pg., 2022-06-11.

Abstract

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-1 alpha, VEGF-A, PTEN expression. Treatment with DOX (1 mu M) significantly increased the number of spheroids (D1), whereas exposure to chemotherapy at 2 mu M on D9 was more effective. DOX treatment resulted in significantly higher expression of VEGF-A, HIF-1 alpha and PIK3CA by D1 and HIF-1 alpha and PTEN were upregulated by D9. Compared to treatment on D1 with D9 (1 mu M) had significantly higher PTEN and lower PIK3CA gene expression. The genes HIF-1 alpha and PTEN were more expressed with 2 mu M of DOX while VEGF-A was downregulated. D1 vs. D9 exhibited reduced VEGF-A, HIF-1 alpha, 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. (AU)

• FAPESP's process: 18/21865-3 - Detection of mutations in liquid biopsy of patients with breast cancer and its response to personalized treatment in organoid culture
• Grantee: Marina Guimarães Gobbo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral