Lactobacilli Differentially Modulate mTOR and Wnt/ β-Catenin Pathways in Different Cancer Cell Lines

Z. Taherian-Esfahani, A. Abedin-Do, Z. Nouri, R. Mirfakhraie, S. Ghafouri-Fard, E. Motevaseli
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引用次数: 36

Abstract

Background Lactobacilli are a group of beneficial bacteria whose anti cancer effects have been evaluated in different cancer cell lines as well as animal models and human subjects. Such anti cancer effects can be exerted via different mechanisms such as modulation of immune response as well as inhibition of pathogens colonization. In addition, lactobacilli have direct cytotoxic effects against cancer cells which may be exerted through modulation of expression cancer related pathways. Objectives The aim of this study is to find the mechanism of anti cancer effects of two lactobacilli strains, Lactobacillus. crispatus (LC) and Lactobacillus. rhamnosus (LR). Materials and Methods We analyzed expression of some mTOR and Wnt/ β-catenin pathways genes in three cancer cell lines (HeLa, MDA-MB-231 and HT-29) following treatment with LC and LR culture supernatants. Results Of note, the expression of CCND1 as a marker of cell proliferation, survival, and angiogenesis, has been decreased following LR treatment in all cell lines. In addition, the expression of SFRP2, an antagonist of Wnt pathway, has been increased in HT-29 following LR treatment and in HeLa cells following LR and LC treatments. Furthermore, we have demonstrated the downregulation of S6K1 expression, a marker of poor prognosis, following LR treatment in HT-29 and following LR and LC treatments in MDA-MB-231 cell line. Conclusions Consequently, lactobacilli can modulate expression of mTOR and Wnt/ β-catenin pathways genes in cancer cell lines in a strain specific as well as cell type specific manner.
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乳酸菌对不同癌细胞mTOR和Wnt/ β-Catenin通路的差异调节
乳酸菌是一类有益细菌,其抗癌作用已在不同的癌细胞系、动物模型和人体中得到了评价。这种抗癌作用可以通过不同的机制发挥作用,如调节免疫反应和抑制病原体定植。此外,乳酸菌对癌细胞具有直接的细胞毒作用,可能通过调节肿瘤相关通路的表达来发挥作用。目的探讨两株乳酸菌的抗癌作用机制。crispatus (LC)和乳酸菌。喂食(LR)。材料和方法我们分析了三种癌细胞(HeLa、MDA-MB-231和HT-29)在LC和LR培养上清处理后mTOR和Wnt/ β-catenin通路部分基因的表达情况。值得注意的是,CCND1的表达作为细胞增殖、存活和血管生成的标志,在LR治疗后,在所有细胞系中都有所下降。此外,在LR处理后的HT-29以及LR和LC处理后的HeLa细胞中,Wnt通路拮抗剂SFRP2的表达增加。此外,我们已经证明,在HT-29和MDA-MB-231细胞系中,LR和LC治疗后,S6K1表达下调,这是预后不良的标志。结论乳酸菌对癌细胞mTOR和Wnt/ β-catenin通路基因的表达具有菌株特异性和细胞类型特异性。
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