PO.ET09.09 · 实验与分子治疗
丁酸盐的选择性细胞毒性凸显其作为靶向抗癌药物的潜力
Selective cytotoxicity of butyrate highlights its potential as a targeted anti-cancer agent
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：在乳腺癌显著的异质性中，三阴性亚型因其高度侵袭性而尤为突出。其缺乏激素受体致使无法采用靶向治疗，凸显了发掘更优治疗策略的必要性。然而，近期研究已认识到丁酸盐作为一种潜在干预药物的价值。丁酸盐是一种微生物来源的短链脂肪酸，具有抗癌作用。我们的初步数据显示，在三阴性细胞系MDA-MB-231中，5 mM浓度的丁酸盐处理可显著降低细胞活力、迁移和增殖。尽管丁酸盐已证实其作为治疗选择的潜力，但其对健康乳腺细胞的安全性仍不明确。因此，本研究在一种非致瘤性乳腺上皮细胞模型（MCF10A）中评估了丁酸盐的作用。
方法：细胞培养于1:1 DMEM/F12培养基中，补充20 ng/mL EGF、0.5 ug/mL氢化可的松、10 ug/mL胰岛素、100 ng/mL霍乱毒素和5%马血清。使用AlamarBlue法测定细胞活力，丁酸盐处理以从800 mM起的系列稀释（1:2）进行，处理时间为24、48和72小时。半最小抑制值（IC-50）通过荧光（590 nm）评估。细胞增殖通过用5 mM丁酸盐处理MCF10A并使用自动细胞计数仪在24、48和72小时进行定量来评价。
结果：未达到IC-50，但在浓度为100 mM及以上时细胞活力有所下降。事实上，MCF10A细胞在5 mM下于24、48和72小时仍保持活力。在所有时间点，5 mM下细胞增殖均无显著变化。
结论：这些结果表明，丁酸盐可降低三阴性乳腺癌细胞的活力，而对MCF10A细胞系的活力无实质性影响，提示存在选择性细胞毒性应答。增殖结果显示，与未处理对照相比，MCF10A在丁酸盐暴露下的细胞生长无显著变化。这些结果显示了丁酸盐作为选择性抗癌药物的潜力，并激发了对丁酸盐调控癌细胞行为机制的研究兴趣。
查看英文原文 English abstract
Background: Within the marked heterogeneity of breast cancer, the triple-negative subtype stands out for its highly aggressive nature. Its absence of hormonal receptors prevents the use of targeted treatments, pointing the need to uncover improved therapeutic strategies. Nevertheless, recent studies have recognized butyrate as a potential agent for intervention. Butyrate is a microbial-derived short chain fatty acid that exerts anti-cancer effects. Our preliminary data showed that butyrate treatment can significantly reduce cell viability, migration, and proliferation at concentrations of 5 mM in the triple-negative cell line MDA-MB-231. While butyrate has proven its potential as a treatment option, its safety towards healthy mammary cells remains unclear. Therefore, in this study, we evaluated the effects of butyrate in a non-tumorigenic mammary epithelial cell model (MCF10A).
Methods: Cells were cultured in 1:1 DMEM/F12 supplemented with 20ng/mL EGF, 0.5 ug/mL hydrocortisone, 10ug/mL insulin, 100ng/mL cholera toxin, and 5% horse serum. Cell viability was measured using AlamarBlue assay, and butyrate treatment was given in serial dilutions (1:2) starting at 800 mM for 24, 48, and 72 hours. The half-minimal inhibitory values (IC-50) were assessed via fluorescence (590nm). Cell proliferation was evaluated by treating MCF10A with 5mM of butyrate and then quantifying for 24, 48, and 72 hours using an automated cell counter.
Results: No IC-50 was reached, yet there was a reduction in cell viability with concentrations from 100 mM and higher. In fact, MCF10A cells continued to be viable at 24, 48, and 72 hours at 5mM. There was no significant change in cell proliferation at 5mM in all time points.
Conclusions: These results suggest that butyrate reduced viability in triple-negative breast cancer cells while having no meaningful effect on the viability of MCF10A cell line, indicating a selective cytotoxic response. Proliferation results show that MCF10A presents no significant change in cell growth upon butyrate exposure in comparison to untreated controls. These results show the potential of butyrate as a selective anti-cancer agent and raise interest in the mechanism of which butyrate modulates cancer cell behavior.
利益披露 Disclosure
N. Yupe-Muñiz, None..
J. Pérez-Santiago, None..
G. Borges-Vélez, None..
E. A. Peterson-Peguero, None..
A. García-Lopez, None..
A. Prats-Marrero, None..
S. B. Abdullah-Vargas, None.