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Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2021 Feb; Vol. 236 (2), pp. 1148-1157. Date of Electronic Publication: 2020 Jul 19. - Publication Year :
- 2021
-
Abstract
- Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.<br /> (© 2020 Wiley Periodicals LLC.)
- Subjects :
- A549 Cells
Animals
Antineoplastic Combined Chemotherapy Protocols pharmacology
Apoptosis drug effects
Autophagy drug effects
Autophagy-Related Protein 5 antagonists & inhibitors
Cell Proliferation drug effects
Fungal Proteins chemistry
Fungal Proteins pharmacology
Ganoderma chemistry
Humans
Immunologic Factors pharmacology
Lung Neoplasms genetics
Lung Neoplasms pathology
Mice
Synthetic Lethal Mutations drug effects
Xenograft Model Antitumor Assays
src-Family Kinases antagonists & inhibitors
Autophagy-Related Protein 5 genetics
Benzodioxoles pharmacology
Caspase 7 genetics
Enzyme Inhibitors pharmacology
Lung Neoplasms drug therapy
Quinazolines pharmacology
src-Family Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 236
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32686156
- Full Text :
- https://doi.org/10.1002/jcp.29924