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基于网络靶点分析与实验验证解析益肺散结丸对非小细胞肺癌的作用及机制

Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation.

作者信息

Yang Hongxing, Guo Qiuyan, Wu Jianbin, Zhong Lixia, Sun Lingling, Liu Wei, Wang Jigang, Lin Lizhu

机构信息

Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Pharmacol. 2022 May 11;13:851554. doi: 10.3389/fphar.2022.851554. eCollection 2022.

Abstract

Non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancer cases, calls for better therapy. Yi-Fei-San-Jie-pill (YFSJ), a well-applicated traditional Chinese medicine formula, was reported to be effective in the treatment of NSCLC. However, its anti-tumor mechanism still needs to be fully elucidated. Herein, a reliable preclinical orthotopic but not subcutaneous model of NSCLC in mice was established to evaluate the anti-cancer properties and further validate the mechanisms of YFSJ. A bioinformatic analysis was executed to identify the potential targets and key pathways of YFSJ on NSCLC. In detail, the anti-tumor effect of YFSJ and the autophagy inhibitor 3-MA was evaluated according to the tumor fluorescence value and comparison of different groups' survival times. As a result, YFSJ markedly decreased tumor size and prolonged survival time in contrast with those in the orthotopic model group ( < 0.05), and it also significantly regulated the protein expression levels of apoptosis- and autophagy-related proteins. In conclusion, this study provides convincing evidence that YFSJ could inhibit the growth of tumors and prolong the survival time of tumor-bearing mice based on the NSCLC orthotopic model, and its anti-tumor effect was closely associated with the promotion of apoptosis and interference of autophagy coupled with regulation of immune infiltration.

摘要

非小细胞肺癌(NSCLC)占肺癌病例的85%,需要更好的治疗方法。益肺散结丸(YFSJ)是一种应用广泛的中药方剂,据报道对NSCLC治疗有效。然而,其抗肿瘤机制仍需充分阐明。在此,建立了一种可靠的小鼠NSCLC原位而非皮下临床前模型,以评估YFSJ的抗癌特性并进一步验证其作用机制。进行了生物信息学分析,以确定YFSJ对NSCLC的潜在靶点和关键途径。具体而言,根据肿瘤荧光值和不同组生存时间的比较,评估了YFSJ和自噬抑制剂3-MA的抗肿瘤作用。结果,与原位模型组相比,YFSJ显著减小了肿瘤大小并延长了生存时间(<0.05),并且还显著调节了凋亡和自噬相关蛋白的表达水平。总之,本研究提供了令人信服的证据,表明基于NSCLC原位模型,YFSJ可以抑制肿瘤生长并延长荷瘤小鼠的生存时间,其抗肿瘤作用与促进凋亡、干扰自噬以及调节免疫浸润密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd92/9130494/5d470375055d/fphar-13-851554-g001.jpg

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