Transcriptomic insight into salinomycin mechanisms in breast cancer cell lines: synergistic effects with dasatinib and induction of estrogen receptor β.

BMC Cancer
Vanessa BellatBenedict Law

Abstract

Tumors are heterogeneous in nature, composed of different cell populations with various mutations and/or phenotypes. Using a single drug to encounter cancer progression is generally ineffective. To improve the treatment outcome, multiple drugs of distinctive mechanisms but complementary anticancer activities (combination therapy) are often used to enhance antitumor efficacy and minimize the risk of acquiring drug resistance. We report here the synergistic effects of salinomycin (a polyether antibiotic) and dasatinib (a Src kinase inhibitor). Functionally, both drugs induce cell cycle arrest, intracellular reactive oxygen species (iROS) production, and apoptosis. We rationalized that an overlapping of the drug activities should offer an enhanced anticancer effect, either through vertical inhibition of the Src-STAT3 axis or horizontal suppression of multiple pathways. We determined the toxicity induced by the drug combination and studied the kinetics of iROS production by fluorescence imaging and flow cytometry. Using genomic and proteomic techniques, including RNA-sequencing (RNA-seq), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western Blot, we subsequently identified the responsible pathways tha...Continue Reading

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Citations

Jan 10, 2021·Pharmacology & Therapeutics·Juntao LiErxi Wu
Aug 13, 2021·Frontiers in Oncology·Hui WangFengfeng Cai

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Datasets Mentioned

BETA
GSE135514

Methods Mentioned

BETA
flow cytometry
Assay
FACS
Fluorescence
RNA-seq
PCR
transfection
fluorescence-activated cell sorting
ESR
protein

Software Mentioned

STAR
Cufflinks
GraphPad Prism
Image Studio Lite
DESeq2
Image Studio
Kaluza
IPA
Ingenuity Pathway Analysis ( IPA
Compusyn

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