Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-γ, interleukin-6, and tumor necrosis factor-α, and suppressed the expression of CD4⁺CD25⁺Foxp3⁺ Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.

中文翻译：

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Akkermansia muciniphila增强顺铂对Lewis肺癌小鼠的抗肿瘤作用。

最近，肠道菌群在肿瘤的发生和发展中起着至关重要的作用，癌症免疫治疗与黏液阿克曼（Akkermansia muciniphila，Akk）之间存在联系。然而，Akk在肺癌中的治疗效果仍不清楚。因此，我们的研究旨在研究顺铂（CDDP）联合Akk对肺癌的抗肿瘤作用。使用皮下接种Lewis肺癌模型的鼠肺癌模型，将50只小鼠分为五组：正常，模型，CDDP，CDDP + Akk和CDDP +抗生素。在5周内治疗后，与模型组相比，给药组改善了肿瘤病理形态学的变化。与CDDP组相比，CDDP与Akk联合可减慢肿瘤体积的生长，下调ki-67，p53，γ，白介素6和肿瘤坏死因子α抑制小鼠外周血和脾脏CD4 ⁺ CD25 ⁺ Foxp3 ⁺ Treg的表达。此外，转录组分析表明，Akk与CDDP结合可明显提高IFI27l2和IGFBP7的水平，并且与细胞因子-细胞因子受体相互作用，Th17细胞分化，FOXO，JAK-STAT和PI3K-Akt信号传导途径有关。这些结果表明，Akk和CDDP的联合治疗的疗效优于唯一的CDDP治疗，其可以增强免疫调节，将是治疗肺癌的有前途的策略。