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蒲公英总黄酮通过调节免疫功能抑制非小细胞肺癌。

Total flavonoids of Taraxacum mongolicum inhibit non-small cell lung cancer by regulating immune function.

机构信息

National International Cooperation Base of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.

National International Cooperation Base of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China; Academy of Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, 450046, China.

出版信息

J Ethnopharmacol. 2021 Dec 5;281:114514. doi: 10.1016/j.jep.2021.114514. Epub 2021 Aug 9.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Taraxacum mongolicum Hand.-Mazz. has been used in lung cancer treatment in Chinese medicine. However, its specific mechanism of action has not yet been reported, and developing pharmaceutical anti-cancer resources is important. Here, we aimed to elucidate the anti-tumor effects of dandelion in vitro and in vivo and assess its effects on immune function in lung cancer patients.

AIM OF THE STUDY

In the present study, we mainly observed the therapeutic effects of total flavonoids from Taraxacum mongolicum Hand.-Mazz. (TFTM) on non-small cell lung cancer and its influence on the body's immune function.

MATERIALS AND METHODS

In vitro experiments on A549 and H1299 cells were performed using the CCK8 method; the proliferation and migration of cells were observed to investigate the wound healing effects of TFTM, and flow cytometry was used to detect the apoptotic rate of TFTM on lung cancer cells. In vivo experiments were preformed to establish a non-small cell lung cancer mouse model using subcutaneously transplanted Lewis cells, and the body weight and tumor growth of the mice were recorded. Hematoxylin and eosin staining was performed for tumor tissue to assess pathological changes. The thymus, spleen, and lungs were isolated for to calculate organ index. The CD4, CD8, and CD4/CD8 levels were detected in mouse spleen using flow cytometry, and IL-2, IL-3, IFN-γ, and TNF-α levels were determined in serum using enzyme-linked immunosorbent assay. Expressions of IL-2, IL-3, IFN-γ, and TNF-α were detected using quantitative real-time PCR in tumor tissues, and Ki67 expression was observed by immunofluorescence.

RESULTS

At 24 h, TFTM (100 and 200 μg/mL) had the best inhibitory effect on the proliferation of A549 and H1299 cells. The cell migration rate significantly reduced (P < 0.01), and the tumor inhibition rate increased (P < 0.01) and promoted apoptosis (P < 0.01). The mouse thymus index significantly increased (P < 0.05) and mouse spleen index reduced (P < 0.05). The CD4, CD8, and CD4/CD8 levels in Lewis lung cancer mouse model increased, as did the levels of IL-2, IL-3, IFN-γ, and TNF-α in the serum and tumor of mice; Ki67 expression in tumor tissues significantly reduced (P < 0.01).

CONCLUSION

TFTM has an inhibitory effect on lung cancer. The mechanism may be that it improves the host's protective immune response by having a milder tumor growth inhibitory effect than cyclophosphamide.

摘要

民族药理学相关性

蒲公英已被用于中医治疗肺癌。然而,其具体的作用机制尚未报道,开发抗癌药物资源非常重要。本研究旨在阐明蒲公英在体外和体内的抗肿瘤作用,并评估其对肺癌患者免疫功能的影响。

研究目的

本研究主要观察蒲公英总黄酮(TFTM)对非小细胞肺癌的治疗作用及其对机体免疫功能的影响。

材料与方法

采用 CCK8 法进行 A549 和 H1299 细胞体外实验;观察细胞的增殖和迁移,以研究 TFTM 的促愈合作用;采用流式细胞术检测 TFTM 对肺癌细胞的凋亡率。建立 Lewis 细胞皮下移植的非小细胞肺癌小鼠模型进行体内实验,记录小鼠的体重和肿瘤生长情况。对肿瘤组织进行苏木精-伊红染色,评估病理变化。分离胸腺、脾脏和肺脏,计算器官指数。采用流式细胞术检测小鼠脾脏中 CD4、CD8 和 CD4/CD8 水平,采用酶联免疫吸附试验检测血清中 IL-2、IL-3、IFN-γ 和 TNF-α 水平。采用实时荧光定量 PCR 检测肿瘤组织中 IL-2、IL-3、IFN-γ 和 TNF-α 的表达,采用免疫荧光法观察 Ki67 的表达。

结果

在 24 小时时,TFTM(100 和 200μg/mL)对 A549 和 H1299 细胞的增殖抑制作用最好。细胞迁移率显著降低(P<0.01),肿瘤抑制率增加(P<0.01)并促进细胞凋亡(P<0.01)。小鼠胸腺指数显著升高(P<0.05),小鼠脾脏指数降低(P<0.05)。Lewis 肺癌小鼠模型中 CD4、CD8 和 CD4/CD8 水平升高,血清和肿瘤中 IL-2、IL-3、IFN-γ 和 TNF-α 水平升高;肿瘤组织中 Ki67 表达显著降低(P<0.01)。

结论

TFTM 对肺癌具有抑制作用。其机制可能是通过比环磷酰胺更温和的肿瘤生长抑制作用来提高宿主的保护性免疫反应。

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