A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells

Abstract

Breast cancer exhibits the highest incidence of all cancer types and is the 2nd leading cause of cancer mortality in women. Up to 82% of breast cancer patients receive a chemotherapy-containing treatment regimen. However, numerous breast tumors recur within 10 years following an initial response and are frequently resistant to previous therapeutic agents. Thus, to analyze the crucial factors, and whether the development of resistance in tumor cells follows certain patterns, is of great importance. In the present study, the clinical treatment schedule of the frequently used chemotherapeutic drug doxorubicin was applied in an in vitro model, the Molecular Evolution Assay (MEA), leading to resistance formation. By investigating the alterations in protein expression in MCF-7 breast cancer cells with three biological replicates, it was observed that the development of resistance to doxorubicin is a multi-directed process. The number and composition of the differentially expressed proteins varied, in addition to the pathways involved in chemoresistance, leading to only a small number of proteins and pathways being commonly regulated in all the MEAs. The proteins 60S ribosomal export protein NMD3 and 4F2 cell-surface antigen heavy chain (SLC3A2) were identified to be the most promising differentially expressed targets; the gene ontology term 'apoptotic signaling pathway' was reduced and 'cell redox homeostasis' was upregulated. Based on the present findings in vitro, it may be hypothesized that the development of resistance in patients is an even more complex process, emphasizing the need for further investigations of resistance development in the clinic to eventually improve patient outcomes.

High methionyl–tRNA synthetase expression predicts poor prognosis in patients with breast cancer

“…Despite remarkable advances in early screening and detection of cancer over the past decades, advanced BC remains a threat to both premenopausal, perimenopausal and postmenopausal women globally due to the development of drug resistance in vivo, 23 with potential tumour recurrence following the initial response. 24 …”

“…Despite remarkable advances in early screening and detection of cancer over the past decades, advanced BC remains a threat to both premenopausal, perimenopausal and postmenopausal women globally due to the development of drug resistance in vivo, 23 with potential tumour recurrence following the initial response. 24 The current treatment targets to reduce the metastatic potentials of invasive BC cells mainly focus on the inhibition of the proliferation-related and invasion-related pathways, including cell cycle, apoptosis and mitosis through chemotherapy, radiotherapy and surgical interventions. 23 25 26 However, the current therapeutic options for BC lack the ability to fully block the fundamental mechanism associated with cancer invasive disseminations.…”

FTIR spectra signatures reveal different cellular effects of EGFR inhibitors on nonsmall cell lung cancer cells

“…Moreover, FTIR is able to isolate specific patterns or chemical fingerprints for distinguishing parental and drug‐resistant cells . Proteomic techniques have also been widely used to determine drug mechanisms . Before samples are subjected to mass spectroscopy, samples must be accurately prepared using multiple steps in laboratory conditions.…”

Laboratory Models for Investigating Breast Cancer Therapy Resistance and Metastasis

“…These resistant cell lines were characterized by metabolic reprogramming that may provide novel therapeutic opportunities for treating chemoresistant TNBCs. Other studies of acute chemotherapy treatment of MCF7 cells revealed increased expression of proteins related to apoptosis signaling and redox homeostasis ( 110 ). Serial analyses of pre- and post-chemotherapy TNBC biopsies has nominated putative drivers and suppressors of adaptive survival programs in post-chemotherapy residual disease.…”