Metronomic doses and drug schematic combination response tested within chambered coverslips for the treatment of breast cancer cells (JIMT-1)

PLoS One. 2022 Sep 29;17(9):e0274911. doi: 10.1371/journal.pone.0274911. eCollection 2022.

Abstract

Low-dose metronomic (LDM) chemotherapy is an alternative to conventional chemotherapy and is the most frequently used approach in low dose chemotherapy regimens. The selection of patients, drug dosages, and dosing intervals in LDM is empirical. In this study, we systematically examined the schedule-dependent interaction of drugs on a breast cancer cell line (BCC) cultured in chambered coverslips. The LDM studies were combined with cell staining in order to better characterize different cell states and cell death modes, including caspase-dependent apoptosis, caspase-independent cell death and autophagy-dependent cell death. Microscope images were examined using the Fiji Trainable Weka Segmentation plugin to analyse cell area in 7500 images showing different modes of cell death. Paclitaxel combined with LDM chemotherapy demonstrated a reduction in the area covered by live cells. In contrast, there was an induction of high levels of cell death due to caspase-dependent apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Caspases
  • Drug Combinations
  • Female
  • Humans
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use

Substances

  • Drug Combinations
  • Caspases
  • Paclitaxel

Grants and funding

The authors thank the financial support from CONICET (PIP2015), ANPCyT (PICT-STARTUP 3772), Biothera Foundation and Florencio Fiorini grant. Lighthouse Core Facility is supported by the following project numbers (Medical Faculty, University of Freiburg - 2021/A2-Fol and - 2021/B3-Fol; DFG - 450392965). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.