Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92617, USA
Department of Mathematics, University of California, Rowland Hall, Irvine, CA 92617, USA.
J R Soc Interface. 2017 Sep;14(134). doi: 10.1098/rsif.2017.0374.
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 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 settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection.
阿司匹林已被证实可降低结直肠癌（CRC）的发病风险，但其中的具体机制尚未完全阐明。在之前的研究中，我们定量分析了不同 CRC 肿瘤细胞系在不同剂量阿司匹林作用下的生长动力学，测量了细胞分裂和细胞死亡的速度。在此基础上，我们使用这些测量参数来计算肿瘤细胞克隆扩展成功的概率，并确定在有无阿司匹林的情况下肿瘤细胞系的进化潜力。计算结果表明，阿司匹林增加了单个肿瘤细胞无法成功克隆扩展的概率。此外，计算结果表明，阿司匹林增加了正在扩张的肿瘤细胞菌落的进化潜力。与未经阿司匹林处理而生长的相同大小的细胞群体相比，经阿司匹林处理的肿瘤细胞群体预计会积累更多的突变（因此更具毒性，更难以治疗）。这表明通过化学预防来延迟癌症的发生和增加其进化潜力之间存在潜在的权衡。需要进一步的研究来确定这些发现在多大程度上适用于特定环境，以及在多大程度上促进了已被流行病学证实的阿司匹林介导的保护作用。
