从传统乳制品中分离出的乳酸杆菌发酵产物 Ab.RS22 可抑制 HeLa 宫颈癌细胞增殖,并通过 PTEN-Akt 通路调节细胞凋亡。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2023.72825.15846
Abbas Asoudeh-Fard, Mitra Salehi, Dariush Ilghari, Asghar Parsaei, Peyman Heydarian, Hossein Piri
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引用次数: 0

摘要

目的:值得注意的是,从乳制品中分离出的乳酸杆菌和双歧杆菌等益生菌对癌细胞有显著的治疗作用。在此,我们评估了从传统乳制品中分离的发酵乳杆菌 Ab.RS22 在体外对 HeLa 宫颈癌细胞的抗增殖和凋亡作用:用0.5、0.75、1、1.5和2 ng/ml浓度的乳酸菌上清液处理HeLa细胞,用溴化四氮唑检测其活力和IC50值。通过反转录聚合酶链式反应(qRT-PCR)定量评估 Caspase-3、P53、PTEN 和 AKT 基因的表达,证实了流式细胞仪检测到的 L. fermentum Ab.RS22 诱导的细胞死亡:结果:乳酸菌对 HeLa 细胞的细胞毒性作用在 24 小时内为 2 纳克/毫升(P50 值为 1.5 纳克/毫升)。流式细胞仪检测结果显示,24 小时内浓度为 1.5 毫微克/毫升的发酵乳杆菌 Ab.RS22 会增加细胞凋亡和坏死的比例。乳酸菌诱导的细胞死亡通过实时荧光定量PCR检测结果得到了验证,Caspase-3、P53和PTEN基因的表达量增加了,而PAKT基因(抗凋亡)的表达量减少了:我们的研究结果表明,L. fermentum Ab.RS22 可以剂量依赖性地抑制 HeLa 细胞的增殖。其凋亡效应通过调节 PTEN/p53/Akt 基因表达和激活 caspase-3 介导的凋亡途径得到证实。因此,在后续研究中,L. fermentum Ab.RS22可被认为是一种有价值的抗癌候选物质,可抑制宫颈癌的发展。
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Isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products inhibits HeLa cervical cancer cell proliferation and modulates apoptosis by the PTEN-Akt pathway.

Objectives: It is worthwhile to note that, some probiotics such as Lactobacilli and Bifidobacteria isolated from dairy products have significant therapeutic effects against cancer cells. Here, we evaluated anti-proliferation and the apoptotic effects of isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products on the HeLa cervical cancer cells in vitro.

Materials and methods: The viability of treated HeLa cells with supernatant of Lactobacillus in 0.5, 0.75, 1, 1.5, and 2 ng/ml concentrations, and IC50 values were detected by tetrazolium bromide. The L. fermentum Ab.RS22-induced cell death by flow cytometry was confirmed through evaluation of the expression of caspase-3, P53, PTEN, and AKT genes by quantitative reverse transcription-polymerase chain reactions (qRT-PCR).

Results: Most cytotoxicity effects of Lactobacillus on HeLa cells were detected in 2 ng/ml at 24 hr (P<0.01); also, the IC50 value was measured as 1.5 ng/ml. The findings of the flow cytometry assay showed that L. fermentum Ab.RS22 in 1.5 ng/ml concentration at 24 hr increased the percentage of both apoptosis and necrosis cells. Lactobacillus-induced cell death was verified through results of Real-time PCR; where expression of caspase-3, P53, and PTEN genes was increased (P<0.01), and also expression of AKT gene (anti-apoptotic) was decreased (P<0.05).

Conclusion: Our findings showed that L. fermentum Ab.RS22 could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating PTEN/p53/Akt gene expression and activation of the caspase-3 mediated apoptosis pathway. Therefore, L. fermentum Ab.RS22 can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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