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Article Dans Une Revue Scientific Reports Année : 2018

Universal response in the RKO colon cancer cell line to distinct antimitotic therapies

Résumé

Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.
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Dates et versions

hal-02318025 , version 1 (16-10-2019)

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Alexander Lorz, Dana-Adriana Botesteanu, Doron Levy. Universal response in the RKO colon cancer cell line to distinct antimitotic therapies. Scientific Reports, 2018, 8, pp.8979. ⟨10.1038/s41598-018-27267-7⟩. ⟨hal-02318025⟩
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