Aidi Injection Inhibits the Migration and Invasion of Gefitinib-resistant Lung Adenocarcinoma Cells by Regulating the PLAT/FAK/AKT Pathway

Overview

Journal Chin Med

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2025 Jan 3

PMID 39754146

Authors

Jingyuan Zhang

Siyun Yang

Xiaodong Chen

Fanqin Zhang

Siyu Guo

Chao Wu

Tieshan Wang

Haojia Wang

Shan Lu

Chuanqi Qiao

Xiaoguang Sheng

Shuqi Liu

Xiaomeng Zhang

Hua Luo

Qinglin Li

Jiarui Wu

Affiliations

Soon will be listed here.

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.

Citing Articles

Traditional Chinese medicine in lung cancer treatment.

Xi Z, Dai R, Ze Y, Jiang X, Liu M, Xu H Mol Cancer. 2025; 24(1):57.

PMID: 40001110 PMC: 11863959. DOI: 10.1186/s12943-025-02245-6.

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

Zhang J, Yang S, Chen X, Zhang F, Guo S, Wu C Chin Med. 2025; 20(1):20.

PMID: 39930460 PMC: 11809022. DOI: 10.1186/s13020-025-01070-9.

References

Siegel R, Miller K, Wagle N, Jemal A . Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1):17-48. DOI: 10.3322/caac.21763. View

Xia C, Dong X, Li H, Cao M, Sun D, He S . Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022; 135(5):584-590. PMC: 8920425. DOI: 10.1097/CM9.0000000000002108. View

Zheng R, Chen R, Han B, Wang S, Li L, Sun K . [Cancer incidence and mortality in China, 2022]. Zhonghua Zhong Liu Za Zhi. 2024; 46(3):221-231. DOI: 10.3760/cma.j.cn112152-20240119-00035. View

Thai A, Solomon B, Sequist L, Gainor J, Heist R . Lung cancer. Lancet. 2021; 398(10299):535-554. DOI: 10.1016/S0140-6736(21)00312-3. View

Gridelli C, Rossi A, Carbone D, Guarize J, Karachaliou N, Mok T . Non-small-cell lung cancer. Nat Rev Dis Primers. 2016; 1:15009. DOI: 10.1038/nrdp.2015.9. View

Bathini S, Raju D, Badilescu S, Kumar A, Ouellette R, Ghosh A . Nano-Bio Interactions of Extracellular Vesicles with Gold Nanoislands for Early Cancer Diagnosis. Research (Wash D C). 2019; 2018:3917986. PMC: 6750071. DOI: 10.1155/2018/3917986. View

Zheng D, Chen Y, Ai S, Zhang R, Gao Z, Liang C . Tandem Molecular Self-Assembly Selectively Inhibits Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress. Research (Wash D C). 2020; 2019:4803624. PMC: 6944487. DOI: 10.34133/2019/4803624. View

Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F . Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994; 106(3):861-5. DOI: 10.1378/chest.106.3.861. View

Schiller J, Harrington D, Belani C, Langer C, Sandler A, Krook J . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346(2):92-8. DOI: 10.1056/NEJMoa011954. View

10.

Wu Y, Zhong W, Li L, Zhang X, Zhang L, Zhou C . Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol. 2007; 2(5):430-9. DOI: 10.1097/01.JTO.0000268677.87496.4c. View

11.

Janne P, Engelman J, Johnson B . Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol. 2005; 23(14):3227-34. DOI: 10.1200/JCO.2005.09.985. View

12.

Spinella M . The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev. 2002; 7(2):130-7. View

13.

Morgensztern D, Campo M, Dahlberg S, Doebele R, Garon E, Gerber D . Molecularly targeted therapies in non-small-cell lung cancer annual update 2014. J Thorac Oncol. 2014; 10(1 Suppl 1):S1-63. PMC: 4346098. DOI: 10.1097/JTO.0000000000000405. View

14.

Lacouture M, Sibaud V . Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails. Am J Clin Dermatol. 2018; 19(Suppl 1):31-39. PMC: 6244569. DOI: 10.1007/s40257-018-0384-3. View

15.

Widakowich C, de Castro Jr G, de Azambuja E, Dinh P, Awada A . Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist. 2008; 12(12):1443-55. DOI: 10.1634/theoncologist.12-12-1443. View

16.

Boumahdi S, de Sauvage F . The great escape: tumour cell plasticity in resistance to targeted therapy. Nat Rev Drug Discov. 2019; 19(1):39-56. DOI: 10.1038/s41573-019-0044-1. View

17.

Zhou S, Deng M, Bian X, Shi J, Liang R, Tao M . Synergistic anti-tumor effects of lenalidomide and gefitinib by upregulating ADRB2 and inactivating the mTOR/PI3K/AKT signaling pathway in lung adenocarcinoma. Cell Mol Biol (Noisy-le-grand). 2024; 70(2):120-127. DOI: 10.14715/cmb/2024.70.2.17. View

18.

Yang J, Qin G, Luo M, Chen J, Zhang Q, Li L . Reciprocal positive regulation between Cx26 and PI3K/Akt pathway confers acquired gefitinib resistance in NSCLC cells via GJIC-independent induction of EMT. Cell Death Dis. 2015; 6:e1829. PMC: 4650742. DOI: 10.1038/cddis.2015.197. View

19.

Li H, Schmid-Bindert G, Wang D, Zhao Y, Yang X, Su B . Blocking the PI3K/AKT and MEK/ERK signaling pathways can overcome gefitinib-resistance in non-small cell lung cancer cell lines. Adv Med Sci. 2011; 56(2):275-84. DOI: 10.2478/v10039-011-0043-x. View

20.

Chen S, Zhang G, Shu Q . Yang-Yin-Jie-Du decoction overcomes gefitinib resistance in non-small cell lung cancer via down-regulation of the PI3K/Akt signalling pathway. Pharm Biol. 2021; 59(1):1294-1304. PMC: 8462892. DOI: 10.1080/13880209.2021.1972122. View