Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice

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 antitum...

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Main Authors: Zhuo Chen, Xiang Qian, Shasha Chen, Xiaoxuan Fu, Guanjun Ma, Aiqin Zhang
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/2969287
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author Zhuo Chen
Xiang Qian
Shasha Chen
Xiaoxuan Fu
Guanjun Ma
Aiqin Zhang
author_facet Zhuo Chen
Xiang Qian
Shasha Chen
Xiaoxuan Fu
Guanjun Ma
Aiqin Zhang
author_sort Zhuo Chen
collection DOAJ
description 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.
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institution Kabale University
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spelling doaj-art-20a4b2d6f8e94da980c82352b84c0e4c2025-02-03T06:45:48ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/29692872969287Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer MiceZhuo Chen0Xiang Qian1Shasha Chen2Xiaoxuan Fu3Guanjun Ma4Aiqin Zhang5Institute of Cancer and Basic Medicine (ICBM), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, No. 38, Guangji Road, Hangzhou, 310022 Zhejiang, ChinaInstitute of Cancer and Basic Medicine (ICBM), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, No. 38, Guangji Road, Hangzhou, 310022 Zhejiang, ChinaDepartment of Traditional Chinese Medicine, Taizhou Cancer Hospital, No. 50, Zhenxin Road, Taizhou, 318000 Zhejiang, ChinaInstitute of Cancer and Basic Medicine (ICBM), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, No. 38, Guangji Road, Hangzhou, 310022 Zhejiang, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053 Zhejiang, ChinaInstitute of Cancer and Basic Medicine (ICBM), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, No. 38, Guangji Road, Hangzhou, 310022 Zhejiang, ChinaRecently, 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.http://dx.doi.org/10.1155/2020/2969287
spellingShingle Zhuo Chen
Xiang Qian
Shasha Chen
Xiaoxuan Fu
Guanjun Ma
Aiqin Zhang
Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
Journal of Immunology Research
title Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
title_full Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
title_fullStr Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
title_full_unstemmed Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
title_short Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice
title_sort akkermansia muciniphila enhances the antitumor effect of cisplatin in lewis lung cancer mice
url http://dx.doi.org/10.1155/2020/2969287
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