Sun E, Meng Xiangqi, Kang Zhaoxia, Gu Huimin, Li Mingyu, Tan Xiaobin, Feng Liang, Jia Xiaobin
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2023 Mar 13;14:1123819. doi: 10.3389/fphar.2023.1123819. eCollection 2023.
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 ( < 0.05) and significantly promoted the amount of Muribaculaceae, Lachnospiraceae ( < 0.05) compared with that in the Normal group. However, ZSP groups increased in probiotic strains () and decreased in pathogens (Muribaculaceae, 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.
肺癌是临床常见的恶性肿瘤,其发病率和死亡率位居恶性肿瘤前列。放疗、化疗及手术治疗在肺癌治疗中发挥着重要作用,然而,放疗存在诸多并发症甚至导致部分功能丧失,手术切除后复发率高,化疗药物毒副作用强。中医药在肺癌的预后及改善方面发挥了巨大作用,其中,增升平(ZSP)具有防治肺癌的作用。基于“肠-肺轴”,从“从肠治肺”的角度出发,本研究旨在探讨增升平对肠道物理、生物及免疫屏障的影响,探索其在肺癌防治中的作用。在C57BL/6小鼠中建立Lewis肺癌和乌拉坦诱导的肺癌模型。称量肿瘤、脾脏和胸腺重量,分析抑瘤率、脾脏和胸腺指数。采用酶联免疫吸附测定法检测炎症因子和免疫指标。收集肺和结肠组织,对肺、结肠组织进行苏木精-伊红染色以观察组织病理学损伤。进行免疫组织化学和蛋白质印迹法检测结肠组织中紧密连接蛋白表达及肿瘤组织中Ki67和p53蛋白表达。最后,收集小鼠粪便,采用16SrDNA高通量测序技术研究肠道微生物群的变化。增升平显著降低肿瘤重量,增加脾脏和胸腺指数。它降低Ki67蛋白表达,增加p53蛋白表达。与模型组相比,增升平组降低了血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)水平,增升平组增加了结肠和支气管肺泡灌洗液(BALF)中分泌型免疫球蛋白A(sIgA)的浓度。增升平高剂量组显著增加了ZO-1、闭合蛋白和Claudin-1等紧密连接蛋白水平。与正常组相比,模型组显著降低了(<0.05)的相对丰度,显著增加了毛螺菌科、瘤胃菌科的数量(<0.05)。然而,增升平组益生菌菌株()增加,病原菌(毛螺菌科、瘤胃菌科)减少。与乌拉坦诱导的肺癌小鼠相比,结果显示增升平显著增加了Lewis肺癌小鼠肠道微生物群的多样性和丰富度。增升平通过增强免疫力、保护肠黏膜和调节肠道微生物群在肺癌防治中发挥重要作用。