Shadi Vaziri Seyedeh, Tajbakhsh Elahe, Khamesipour Faham, Momtaz Hassan, Mazaheri Zohre
Department of Microbiology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran.
Rep Biochem Mol Biol. 2024 Jul;13(2):263-272. doi: 10.61186/rbmb.13.2.263.
Breast cancer remains a significant global health concern, with challenges in treating advanced stages necessitating the exploration of novel therapeutic approaches. Bacterial outer membrane vesicles (OMVs) have shown promise in cancer immunotherapy by targeting cancer cells and modulating immune responses. This study investigated the effects of Helicobacter pylori-derived OMVs on the activation of the Snail/β-Catenin gene cascade in regulating inflammation and cell migration in a mouse model of breast cancer.
The OMVs were extracted from the culture of strain 26695 (ATCC 700392) using ultracentrifugation. In the mouse model, the vesicles were injected intraperitoneally into Balb/c mice with breast tumors. Tumor growth was assessed through histological examination of tumor samples. IgA and IgG antibodies were measured using ELISA. The expression of E-cadherin and vimentin proteins was evaluated by immunohistochemistry, and real-time PCR was used for vimentin, Snail, α-SMA, and β-catenin in serum samples from the different groups.
The OMV treatment led to a significant increase in the expression of α-SMA, β-catenin, Snail, and vimentin genes, indicating a potential induction of epithelial-mesenchymal transition and enhanced cancer cell growth. Additionally, a decrease in vimentin expression and an increase in E-cadherin expression were observed, suggesting inhibition of cell migration. The study also revealed alterations in systemic IgA and IgG antibody levels, indicating potential immunomodulatory effects of OMVs.
These findings highlight the therapeutic potential of OMVs derived from in breast cancer treatment by targeting gene cascades involved in cancer progression and modulating immune responses.
乳腺癌仍然是一个重大的全球健康问题，治疗晚期乳腺癌面临挑战，因此需要探索新的治疗方法。细菌外膜囊泡（OMVs）通过靶向癌细胞和调节免疫反应，在癌症免疫治疗中显示出前景。本研究调查了幽门螺杆菌来源的OMVs对乳腺癌小鼠模型中Snail/β-连环蛋白基因级联激活的影响，该基因级联在调节炎症和细胞迁移中起作用。
使用超速离心法从26695菌株（ATCC 700392）的培养物中提取OMVs。在小鼠模型中，将这些囊泡腹腔注射到患有乳腺肿瘤的Balb/c小鼠体内。通过对肿瘤样本进行组织学检查来评估肿瘤生长情况。使用酶联免疫吸附测定法（ELISA）测量IgA和IgG抗体。通过免疫组织化学评估E-钙黏蛋白和波形蛋白的表达，并且使用实时聚合酶链反应（PCR）检测不同组血清样本中波形蛋白、Snail、α-平滑肌肌动蛋白（α-SMA）和β-连环蛋白的表达。
OMV治疗导致α-SMA、β-连环蛋白、Snail和波形蛋白基因的表达显著增加，表明可能诱导上皮-间质转化并促进癌细胞生长。此外，观察到波形蛋白表达减少，E-钙黏蛋白表达增加，这表明细胞迁移受到抑制。该研究还揭示了全身IgA和IgG抗体水平的变化，表明OMVs具有潜在的免疫调节作用。
这些发现突出了幽门螺杆菌来源的OMVs在乳腺癌治疗中的治疗潜力，其通过靶向参与癌症进展基因级联反应并调节免疫反应来发挥作用。
