艾迪注射液通过调节PLAT/FAK/AKT通路抑制吉非替尼耐药肺腺癌细胞的迁移和侵袭。

Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway.

作者信息

Zhang Jingyuan, Yang Siyun, Chen Xiaodong, Zhang Fanqin, Guo Siyu, Wu Chao, Wang Tieshan, Wang Haojia, Lu Shan, Qiao Chuanqi, Sheng Xiaoguang, Liu Shuqi, Zhang Xiaomeng, Luo Hua, Li Qinglin, Wu Jiarui

机构信息

Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

出版信息

Chin Med. 2025 Jan 3;20(1):2. doi: 10.1186/s13020-024-01054-1.

DOI:10.1186/s13020-024-01054-1

PMID:39754146

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11699780/

Abstract

BACKGROUND

With extended gefitinib treatment, the therapeutic effect in some non-small cell lung cancer (NSCLC) patients declined with the development of drug resistance. Aidi injection (ADI) is utilized in various cancers as a traditional Chinese medicine prescription. This study explores the molecular mechanism by which ADI, when combined with gefitinib, attenuates gefitinib resistance in PC9GR NSCLC cells.

METHODS

In vitro and in vivo pharmacological experiments were conducted in PC9GR cells and NSG mice with PC9GR cell-derived tumors, respectively. The molecular mechanism of ADI was further studied using whole-transcriptome sequencing technology. Bioinformatics and molecular biology methods were employed to validate the critical targets of ADI.

RESULTS

Firstly, ADI treatment alone and combined with gefitinib significantly inhibited the proliferation, migration, and invasion of PC9GR cells. Then, whole-transcriptome sequencing and bioinformatics analysis revealed that PLAT is a key target for the increased efficacy of ADI combined with gefitinib. Additionally, ADI downregulates the expression of PLAT, TNC, ITGB3, p-AKT, p-PI3K, and p-FAK. ADI inhibits the migration and invasion of PC9GR cells by regulating the PLAT/FAK/AKT pathway.

CONCLUSIONS

Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway. This study provides essential evidence for elucidating the mechanism of ADI in synergistic therapy for lung cancer.

摘要

背景

随着吉非替尼治疗时间的延长，一些非小细胞肺癌（NSCLC）患者的治疗效果会随着耐药性的产生而下降。艾迪注射液（ADI）作为一种中药方剂，被应用于多种癌症的治疗。本研究探讨了ADI与吉非替尼联合使用时，在PC9GR NSCLC细胞中减弱吉非替尼耐药性的分子机制。

方法

分别在PC9GR细胞和携带PC9GR细胞源性肿瘤的NSG小鼠中进行了体外和体内药理学实验。利用全转录组测序技术进一步研究了ADI的分子机制。采用生物信息学和分子生物学方法验证了ADI的关键靶点。

结果

首先，单独使用ADI治疗以及与吉非替尼联合使用均显著抑制了PC9GR细胞的增殖、迁移和侵袭。然后，全转录组测序和生物信息学分析表明，PLAT是ADI联合吉非替尼疗效增强的关键靶点。此外，ADI下调PLAT、TNC、ITGB3、p-AKT、p-PI3K和p-FAK的表达。ADI通过调节PLAT/FAK/AKT信号通路抑制PC9GR细胞的迁移和侵袭。