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基于网络药理学和实验验证的扶正祛毒方治疗肺癌的机制

Mechanism of Fuzheng Qudu prescription in the treatment of lung cancer based on network pharmacology and experimental validation.

作者信息

Su Binjie, Mao Qiyuan, Li Daorui, Wu Yingyi, Wang Bo, Wang Xueqian

机构信息

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830017, China.

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.

出版信息

Heliyon. 2024 Sep 6;10(18):e37546. doi: 10.1016/j.heliyon.2024.e37546. eCollection 2024 Sep 30.

Abstract

OBJECTIVE

This research utilized network pharmacology to investigate the potential of Fuzheng Qudu prescription (FZQDP) in treating lung cancer (LC).

METHODS

The components and their targets of FZQDP were analyzed for their relationship with LC-related targets using bioinformatics tools. Mouse Lewis lung carcinoma (LLC) cells were cultured and treated with FZQDP or cisplatin (DDP) before applying the MTT assay to determine FZQDP concentrations, and the IC50 value. According to the IC50 value, the effect of FZQDP on apoptosis and cell cycle was detected by flow cytometry. Mouse tumor growth was recorded using live animal imaging, and measurements of tumor and spleen weight were used to calculate the tumor inhibition rate and spleen index. The effects on mouse liver and kidneys were observed by analyzing levels of AST, ALT, BUN, and CRE in blood and hematoxylin and eosin (H & E) stained sections. Additionally, levels of IL-2, IL-10, IL-6, and IFN-γ in serum, along with the frequencies of CD4 and CD8 T cells in the spleen, were measured using Mouse multiple Cytokine Assay and flow cytometry, respectively.

RESULTS

SRC, STAT3, MAPK3, and MAPK1 could be crucial targets of FZQDP in the treatment of LC. FZQDP demonstrated inhibition of LC cell proliferation and tumor growth, as well as enhancement of apoptosis and induction of G2 phase cell cycle arrest. Furthermore, FZQDP led to elevated levels of IL-2 and IFN-γ, increased frequencies of CD4 T cells and decreased levels of IL-6 and IL-10. Importantly, FZQDP did not exhibit any noticeable hepatotoxic or nephrotoxic effects in mice.

CONCLUSION

FZQDP may target multiple signaling pathways to treat LC. In a LC mouse model, FZQDP was found to inhibit tumor growth and improve immune function.

摘要

目的

本研究利用网络药理学探讨扶正祛毒方(FZQDP)治疗肺癌(LC)的潜力。

方法

使用生物信息学工具分析FZQDP的成分及其靶点与LC相关靶点的关系。培养小鼠Lewis肺癌(LLC)细胞,在应用MTT法测定FZQDP浓度和IC50值之前,用FZQDP或顺铂(DDP)处理细胞。根据IC50值,通过流式细胞术检测FZQDP对细胞凋亡和细胞周期的影响。使用活体动物成像记录小鼠肿瘤生长情况,并通过测量肿瘤和脾脏重量来计算肿瘤抑制率和脾脏指数。通过分析血液中AST、ALT、BUN和CRE水平以及苏木精和伊红(H&E)染色切片,观察对小鼠肝脏和肾脏的影响。此外,分别使用小鼠多种细胞因子检测法和流式细胞术测量血清中IL-2、IL-10、IL-6和IFN-γ水平,以及脾脏中CD4和CD8 T细胞的频率。

结果

SRC、STAT3、MAPK3和MAPK1可能是FZQDP治疗LC的关键靶点。FZQDP表现出抑制LC细胞增殖和肿瘤生长的作用,同时增强细胞凋亡并诱导G2期细胞周期停滞。此外,FZQDP导致IL-2和IFN-γ水平升高,CD4 T细胞频率增加,IL-6和IL-10水平降低。重要的是,FZQDP在小鼠中未表现出任何明显的肝毒性或肾毒性作用。

结论

FZQDP可能通过靶向多个信号通路治疗LC。在LC小鼠模型中,发现FZQDP可抑制肿瘤生长并改善免疫功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3323/11416244/295112b4e5c1/gr1.jpg

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