Preprint Communication Version 1 This version is not peer-reviewed

Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality

Version 1 : Received: 28 July 2020 / Approved: 30 July 2020 / Online: 30 July 2020 (09:01:50 CEST)

How to cite: Koshkin, V.; Oliveira, M.B.D.; Peng, C.; Aiiles, L.; Liu, G.; Covens, A.; Krylov, S.N. Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality. Preprints 2020, 2020070709 (doi: 10.20944/preprints202007.0709.v1). Koshkin, V.; Oliveira, M.B.D.; Peng, C.; Aiiles, L.; Liu, G.; Covens, A.; Krylov, S.N. Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality. Preprints 2020, 2020070709 (doi: 10.20944/preprints202007.0709.v1).

Abstract

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

Subject Areas

intrinsic multi-drug resistance; acquired multi-drug resistance; circulating tumor cells; single cells; cell clusters; cell monolayer; multi-cellular spheroids; cytometry of reaction rate constant; ovarian cancer

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