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Effect of aspirin on tumour cell colony formation and evolution

机译:阿司匹林对肿瘤细胞集落形成和进化的影响

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摘要

Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the in vitro growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to in vivo settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection.
机译:已知阿司匹林可降低结直肠癌(CRC)发生的风险,但其潜在机制尚不完全清楚。在先前的研究中,我们量化了用不同剂量的阿司匹林处理的不同CRC肿瘤细胞系的体外生长动力学,测量了细胞分裂和细胞死亡的速率。在这里,我们使用这些测量的参数来计算成功克隆扩增的机会,并确定在存在和不存在阿司匹林的情况下肿瘤细胞系的进化潜力。计算表明阿司匹林增加了单个肿瘤细胞无法克隆扩增的可能性。进一步地,计算表明阿司匹林增加了扩大的肿瘤细胞集落的进化潜力。与没有阿司匹林生长的相同大小的细胞群相比,经阿司匹林处理的肿瘤细胞群预计会导致更多的突变积累(因此更具毒性,更难以治疗)。这表明在延迟癌症发作和通过化学预防增加其进化潜力之间可能存在权衡。进一步的工作需要调查这些发现在多大程度上适用于体内环境,以及它们在何种程度上有助于流行病学上证明的阿司匹林介导的保护作用。

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