Back to Search Start Over

Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells.

Authors :
Chiu LY
Hsin IL
Tsai JN
Chen CJ
Ou CC
Wu WJ
Sheu GT
Ko JL
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.)

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