The RNA disruption assay is superior to conventional drug sensitivity assays in detecting cytotoxic drugs.
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Doxorubicin
/ pharmacology
Drug Discovery
/ methods
Drug Resistance, Neoplasm
/ genetics
Drug Screening Assays, Antitumor
/ methods
Female
Humans
Ovarian Neoplasms
/ drug therapy
Prospective Studies
RNA
/ analysis
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 05 2020
26 05 2020
Historique:
received:
29
12
2019
accepted:
29
04
2020
entrez:
28
5
2020
pubmed:
28
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Conventional drug sensitivity assays used to screen prospective anti-cancer agents for cytotoxicity monitor biological processes associated with active growth and proliferation, used as proxies of cell viability. However, these assays are unable to distinguish between growth-arrested (but otherwise viable) cells and non-viable/dead cells. As a result, compounds selected based on the results of these assays may only be cytostatic, halting or slowing tumour progression temporarily, without tumour eradication. Because agents capable of killing tumour cells (cytotoxic drugs) are likely the most promising in the clinic, there is a need for drug sensitivity assays that reliably identify cytotoxic compounds that induce cell death. We recently developed a drug sensitivity assay, called the RNA disruption assay (RDA), which measures a phenomenon associated with tumour cell death. In this study, we sought to compare our assay's performance to that of current commonly used drug sensitivity assays (i.e, the clonogenic, the cell counting kit-8 and the Trypan blue exclusion assays). We found that RNA disruption occurred almost exclusively when total cell numbers decreased (cytotoxic concentrations), with little to no signal detected until cells had lost viability. In contrast, conventional assays detected a decrease in their respective drug sensitivity parameters despite cells retaining their viability, as assessed using a recovery assay. We also found that the RDA can differentiate between drug-sensitive and -resistant cells, and that it can identify agents capable of circumventing drug resistance. Taken together, our study suggests that the RDA is a superior drug discovery tool, providing a unique assessment of cell death.
Identifiants
pubmed: 32457334
doi: 10.1038/s41598-020-65579-9
pii: 10.1038/s41598-020-65579-9
pmc: PMC7250890
doi:
Substances chimiques
Antineoplastic Agents
0
RNA
63231-63-0
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8671Références
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