PO.ET02.07 · 实验与分子治疗
基于L.paracasei NPB01与L.rhamnosus GG序贯发酵的后生元对乳腺癌发挥抗肿瘤活性
Postbiotic based on sequential fermentation of L.paracasei NPB01 and L.rhamnosus GG exerts antitumor activities against breast cancer
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景。乳腺癌（BC）是全球女性中最常见且致死率最高的癌症。越来越多的证据强调肠道菌群通过多种机制调控乳腺癌风险、治疗反应和复发，这些机制包括产生具有生物活性的化合物和代谢产物。这些来自益生菌发酵的非活性微生物产物和代谢副产物被称为后生元（postbiotics），无需活性微生物即可对宿主发挥有益作用。源自Lacticaseibacillus属的后生元代表了一类具有潜在抗癌特性的新型治疗剂。在本研究中，我们考察了一种创新后生元产品（iPB）在乳腺癌实验模型中的治疗作用，该产品通过L.paracasei NPB01与L.rhamnosus GG序贯发酵开发而成。
方法。使用以下细胞系代表主要乳腺癌亚型：MCF7细胞（ER+/HER2）、MDA-MB-231（三阴性乳腺癌）、SKBR3（HER2+）。以MCF-10A（正常乳腺上皮细胞）、Caco-2（肠上皮细胞）和外周血单个核细胞（PBMC）作为对照。通过集落形成实验评估细胞活力。使用Annexin V/7-AAD染色评估凋亡，通过流式细胞术评估HLA I类分子表面表达，并通过划痕愈合实验评估癌细胞迁移。
结果。从0.5 mg/ml、72 h起，iPB处理使MCF7细胞集落形成减少>50%，MDA-MB-231减少>30%，SKBR3细胞减少>40%（p<0.01）。从0.5 mg/ml、72 h起，iPB增加了所有乳腺癌细胞系的早期和晚期凋亡细胞比率。相反，iPB暴露至5 mg/ml、120 h对对照细胞（MCF-10A、Caco-2、PBMC）的细胞活力无影响。从0.5 mg/ml、72 h剂量起，所有乳腺癌细胞系在iPB暴露后HLA I类表达升高1.20至1.30倍。对照细胞在iPB暴露后HLA I类表达升高幅度较小。iPB暴露抑制了所有乳腺癌细胞模型的细胞迁移过程和炎性细胞因子反应。
结论。iPB降低所有主要乳腺癌表型的细胞活力和细胞迁移。这些作用与所有乳腺癌细胞表型HLA I类表面表达升高相平行，可能增强免疫原性。这些发现提示iPB可能成为乳腺癌治疗和预防中一种有前景的新型药物。
查看英文原文 English abstract
Backgroud. Breast cancer (BC) is the most common and deadly cancer in women worldwide. Emerging evidence highlights the role of gut microbiota in modulating breast cancer risk, treatment response, and recurrence through various mechanisms, including the production of biologically active compounds and metabolites. These non-viable microbial products and metabolic byproducts from probiotic fermentation, known as postbiotics, exert beneficial effects on the host without the need for live microorganisms. Postbiotics derived from Lacticaseibacillus species represent a novel class of therapeutics with potential anti-cancer properties. In this study, we investigated the therapeutic effects of an innovative postbiotic product (iPB), developed through sequential fermentation of L.paracasei NPB01 and L.rhamnosus GG, in BC experimental models.
Methods. The following cell lines were used to represent main BC subtypes: MCF7 cells (ER+/HER2), MDA-MB-231 (triple negative breast cancer), SKBR3 (HER2+). MCF-10A (normal breast epithelial cells), Caco-2 (enterocytes), and peripheral mononuclear blood cells (PBMC) were used as control. Cell viability was assessed by colony formation assay. Apoptosis was evaluated using Annexin V/7-AAD staining, HLA class I surface expression by flow cytometry, and cancer cells migration by wound healing assay.
Results. iPB exposure resulted in >50% colony formation reduction in MCF7, >30% in MDA-MB-231 and >40% in SKBR3 cells starting from 0.5 mg/ml for 72 h ( p <0.01). iPB increased early and late apoptotic cell rate in all BC cell lines starting from 0.5 mg/ml for 72 h. On the contrary, iPB exposure up to 5 mg/ml for 120 h did not affect cell viability in control cells (MCF-10A, Caco-2, PBMC). 1.20 to 1.30 fold increase in HLA class I expression was observed in all BC cell lines after the exposure with iPB starting from the dose of 0.5 mg/ml for 72 h. A less intense HLA class I expression increase was observed in control cells after the iPB exposure. Cell migration process and inflammatory cytokines response were inhibited by the iPB exposure in all BC cell models.
Conclusions. iPB reduces cell viability and cell migration in all main BC phenotypes. These effects parallel with HLA class I surface expression increase in all BC cell phenotypes, potentially enhancing immunogenicity. These findings suggest that iPB may represent a promising novel agent in BC treatment and prevention.
利益披露 Disclosure
R. Berni Canani, None..
C. Luongo, None..
L. Pisapia, None..
F. Oglio, None..
R. Di Santillo, None..
A. Gaeta, None..
C. Scocco, None..
M. Michelini, None..
V. Mauriello, None..
A. Cadavere, None..
C. Messuri, None..
D. Mussallem, None.