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Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice.

ABSTRACT: Chemotherapy is one of the major treatment strategies for esophageal squamous cell carcinoma (ESCC). Unfortunately, most chemotherapeutic drugs have significant impacts on the intestinal microbes, resulting in side effects and reduced efficiency. Therefore, new strategies capable of overcoming these disadvantages of current chemotherapies are in urgent need. The natural product, Cepharanthine hydrochloride (CEH), is known for its anticancer and immunoregulatory properties. By sequencing the V4 region of 16S rDNA, we characterized the microbes of tumor-bearing mice treated with different chemotherapy strategies, including with CEH. We found that CEH improved the therapeutic effect of CDDP by manipulating the gut microbiota. Through metagenomic analyses of the microbes community, we identified a severe compositional and functional imbalance in the gut microbes community after CDDP treatment. However, CEH improved the effect of chemotherapy and ameliorated CDDP treatment-induced imbalance in the intestinal microbes. Mechanically, CEH activated TLR4 and MYD88 innate immune signaling, which is advantageous for the activation of the host's innate immunity to exert a balanced intestinal environment as well as to trigger a better chemotherapeutic response to esophageal cancer. In addition, TNFR death receptors were activated to induce apoptosis. In summary, our findings suggest that chemotherapy of CDDP combined with CEH increased the effect of chemotherapy and reduced the side effects on the microbes and intestinal mucosal immunity. We believe that these findings provide a theoretical basis for new clinical treatment strategies.

SUBMITTER: Zhou P

PROVIDER: S-EPMC6606789 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice.

Zhou Pengjun P Li Ziyao Z Xu Dandan D Wang Ying Y Bai Qi Q Feng Yue Y Su Guifeng G Chen Pengxiao P Wang Yao Y Liu Huizhong H Wang Xiaogang X Zhang Rong R Wang Yifei Y

Frontiers in cellular and infection microbiology 20190626

Chemotherapy is one of the major treatment strategies for esophageal squamous cell carcinoma (ESCC). Unfortunately, most chemotherapeutic drugs have significant impacts on the intestinal microbes, resulting in side effects and reduced efficiency. Therefore, new strategies capable of overcoming these disadvantages of current chemotherapies are in urgent need. The natural product, Cepharanthine hydrochloride (CEH), is known for its anticancer and immunoregulatory properties. By sequencing the V4 r ...[more]

PMID: 31293986

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Project description:Lung cancer is a common malignant tumor in clinical practice, and its morbidity and mortality are in the forefront of malignant tumors. Radiotherapy, chemotherapy, and surgical treatment play an important role in the treatment of lung cancer, however, radiotherapy has many complications and even causes partial loss of function, the recurrence rate after surgical resection is high, and the toxic and side effects of chemotherapy drugs are strong. Traditional Chinese medicine has played a huge role in the prognosis and improvement of lung cancer, among them, Zengshengping (ZSP) has the effect of preventing and treating lung cancer. Based on the "gut-lung axis" and from the perspective of "treating the lung from the intestine", the purpose of this study was to research the effect of Zengshengping on the intestinal physical, biological, and immune barriers, and explore its role in the prevention and treatment of lung cancer. The Lewis lung cancer and urethane-induced lung cancer models were established in C57BL/6 mice. The tumor, spleen, and thymus were weighed, and the inhibition rate, splenic and thymus indexes analyzed. Inflammatory factors and immunological indexes were detected by enzyme-linked immunosorbent assay. Collecting lung and colon tissues, hematoxylin and eosin staining was performed on lung, colon tissues to observe histopathological damage. Immunohistochemistry and Western blotting were carried out to detect tight junction protein expression in colon tissues and expression of Ki67 and p53 proteins in tumor tissues. Finally, the feces of mice were collected to investigate the changes in intestinal microbiota using 16SrDNA high-throughput sequencing technology. ZSP significantly reduced tumor weight and increased the splenic and thymus indexes. It decreased expression of Ki67 protein and increased expression of p53 protein. Compared with Model group, ZSP group reduced the serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and ZSP group increased the concentration of secretory immunoglobulin A (sIgA) in the colon and the bronchoalveolar lavage fluid (BALF). ZSPH significantly increased the level of tight junction proteins such as ZO-1, Occludin and Claudin-1. Model group significantly reduced the relative abundance of Akkermansia (p < 0.05) and significantly promoted the amount of norank_f_Muribaculaceae, norank_f_Lachnospiraceae (p < 0.05) compared with that in the Normal group. However, ZSP groups increased in probiotic strains (Akkermansia) and decreased in pathogens (norank_f_Muribaculaceae, norank_f_Lachnospiraceae). Compared with the urethane-induced lung cancer mice, the results showed that ZSP significantly increased the diversity and richness of the intestinal microbiota in the Lewis lung cancer mice. ZSP played an important role in the prevention and treatment of lung cancer by enhancing immunity, protecting the intestinal mucosa and regulating the intestinal microbiota.

Dataset Information

Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice.

Publications

Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice.

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