PO.ET09.09 · 实验与分子治疗
己酸盐对三阴性乳腺癌致癌表型的抑制作用
Inhibition of oncogenic phenotypes by hexanoate in triple-negative breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：三阴性乳腺癌（TNBC）是乳腺癌的一种侵袭性分子亚型，其定义为缺乏雌激素和孕激素受体，以及不存在HER2扩增。这种分子特征限制了当前的治疗选择，导致患者预后不良。近期证据凸显微生物组是癌症生物学中的一个关键因素，可通过代谢物和细菌产物调节肿瘤进展。在这些产物中，中链脂肪酸（MCFAs），如己酸盐，是由微生物组内的微生物发酵产生的。我们实验室先前的研究表明，己酸盐可降低口腔癌细胞的活力和增殖能力，这可能提示己酸盐是替代性癌症治疗的一个有前景的候选靶点。因此，本研究的目的是评估己酸盐对TNBC细胞系MDA-MB-231的致癌表型（包括细胞活力、增殖和迁移）的影响。
方法：MDA-MB-231细胞在37°C、5% CO2的RPMI培养基中培养。使用AlamarBlue在用己酸钠处理24、48和72小时（h）后测量细胞活力，采用9个不同浓度（起始为800mM，1:2系列稀释）以测定半数最大抑制浓度（IC50）。细胞增殖通过每孔接种100,000个细胞并用TrypanBlue计数在5mM己酸盐处理24h、48h和72h后细胞数量的变化来测量。细胞迁移通过划痕试验评估；造成伤口后，在0h、24h和48h测量其宽度以计算伤口闭合百分比。
结果：己酸盐在24h、48h和72h降低了细胞活力，IC50稳定为29mM。此外，用己酸盐处理24h和48h时未观察到对增殖率的显著影响，而在72h时则显著下降（p=0.004）。此外，己酸盐在两个时间点均显示出伤口闭合百分比的下降，在48h时具有显著性（p = 0.002）。
结论：总体而言，己酸盐对TNBC细胞的活力、增殖和迁移表现出抑制作用。作为一种与微生物组相关的化合物，己酸盐可能以时间依赖性方式调节癌细胞行为，并可能成为TNBC治疗的一个潜在替代靶点，尽管仍需进一步研究加以验证。
查看英文原文 English abstract
Background: Triple-Negative Breast Cancer (TNBC) is an invasive molecular subtype of breast cancer defined by the lack of estrogen and progesterone receptors, and the absence of HER2 amplification. This molecular profile limits current treatment options contributing to poor patient outcomes. Recent evidence features the microbiome as a key factor in cancer biology, modulating tumor progression through metabolites and bacterial products. Among these products, medium-chain fatty acids (MCFAs), such as hexanoate, are produced by microbial fermentation within the microbiome. Previous studies from our laboratory demonstrated that hexanoate reduces the viability and proliferative capacity in oral cancer cells, which may suggest hexanoate as a promising candidate target for alternative cancer treatments. Therefore, the aim of this study was to evaluate the impact of hexanoate on oncogenic phenotypes including cell viability, proliferation, and migration of the TNBC cell line MDA-MB-231.
Methods: MDA-MB-231 cells were cultured at 37°C, 5% CO 2 in RPMI-media. Cell viability was measured using AlamarBlue after 24, 48 and 72 hours (h) of treatment with sodium hexanoate at 9 different concentrations starting at 800mM (1:2 serial dilution) to measure the half-minimal inhibitory concentration (IC50). Cell proliferation was measured by seeding 100,000 cells per well and counting with TrypanBlue the change in cell number after treatment with hexanoate at 5mM for 24h, 48h and 72h. Cell migration was evaluated using a scratch assay; after inflicting a wound, its width was measured at 0h, 24h, and 48h to calculate the percentage of wound closure.
Results: Hexanoate reduced cell viability at 24h, 48h, and 72h with a consistent IC50 of 29mM. Additionally, no significant effects on the proliferation rate were observed at 24h and 48h when treated with hexanoate, whereas it decreased significantly at 72h (p=0.004). Furthermore, hexanoate showed a decreased percentage of wound closure at both time points, showing significance at 48h (p = 0.002).
Conclusions: Overall, hexanoate exhibited inhibitory effects on viability, proliferation, and migration in TNBC cells. As a microbiome-associated compound, hexanoate may modulate cancer cell behavior in a time-dependent manner and represent a potential alternative target for TNBC treatment, although additional studies are required for validation.
利益披露 Disclosure
N. Yupe-Muñiz, None..
S. B. Abdullah-Vargas, None..
O. A. Loperena-González, None..
A. S. García- López, None..
G. Borges-Vélez, None..
J. Pérez-Santiago, None.