Enhancing the Therapeutic Efficacy of Gefitinib in Human Non-Small-Cell Lung Cancer through Drug Combination

Autor: Jian-Hua Gong, Meng-Ran Zhang, Xiujun Liu, Jian Xu, Hao Cai, Yue Du, Yue-Xuan Wang
Rok vydání: 2021
Předmět:
Lung Neoplasms
Pharmaceutical Science
Apoptosis
Mice
SCID
02 engineering and technology
medicine.disease_cause
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Mice
Inbred NOD
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
Drug Discovery
Epidermal growth factor receptor
Mice
Inbred BALB C
biology
Cell Cycle
Drug Synergism
Gefitinib
021001 nanoscience & nanotechnology
ErbB Receptors
Drug Combinations
Molecular Medicine
Female
Growth inhibition
0210 nano-technology
Signal Transduction
medicine.drug
Combination therapy
Mice
Nude
03 medical and health sciences
Cell Line
Tumor
Pancreatic cancer
medicine
Animals
Humans
Lung cancer
Protein Kinase Inhibitors
Cell Proliferation
Tumor microenvironment
business.industry
medicine.disease
respiratory tract diseases
chemistry
Drug Resistance
Neoplasm
Cancer research
biology.protein
Carcinogenesis
business
Zdroj: Molecular Pharmaceutics. 18:1397-1407
ISSN: 1543-8392
1543-8384
Popis: The interaction between tumor cells and the tumor microenvironment (TME) significantly influences tumorigenesis, so TME-targeted therapy has attracted widespread attention. We have previously demonstrated that the combination of dipyridamole, bestatin, and dexamethasone (DBD mix, DBDx) is effective against heterogeneous human pancreatic cancer and hepatocellular carcinoma in mouse xenograft models. To further expand the therapeutic potential of this drug combination, herein, we investigated the antitumor efficacy and the underlying mechanism of DBDx and the combination of DBDx and gefitinib in different mouse xenograft models of human non-small-cell lung cancer (NSCLC). Three human cancer cell lines H460, PG, and A431 were used to determine the apoptosis and growth inhibition induced by DBDx, gefitinib, and their combinations. Changes in epidermal growth factor receptor (EGFR) signaling pathway-related proteins were analyzed following treatment using western blotting. In vitro, DBDx strongly inhibited the proliferation of tumor cells, whereas the combined treatment exhibited a significant synergistic effect. Compared with DBDx, the combination treatment further induced apoptosis and downregulated the expression of molecules associated with EGFR signaling pathway. In vivo, compared with DBDx alone, the combination treatment distinctly inhibited tumor growth in mouse xenograft models of human NSCLC. Overall, our results indicate that the combination of DBDx and gefitinib in the treatment of human NSCLC is very promising, which warrants further translational studies.
Databáze: OpenAIRE
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