RRC ID 74515
Author Xu Y, Afify SM, Du J, Liu B, Hassan G, Wang Q, Li H, Liu Y, Fu X, Zhu Z, Chen L, Seno M.
Title The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells.
Journal Sci Rep
Abstract Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3Kγ inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3Kγ, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.
Volume 12(1)
Pages 347
Published 2022-1-10
DOI 10.1038/s41598-021-04265-w
PII 10.1038/s41598-021-04265-w
PMID 35013447
PMC PMC8748513
MeSH Animals Apoptosis / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Cell Self Renewal / drug effects Class Ib Phosphatidylinositol 3-Kinase / metabolism* ErbB Receptors / antagonists & inhibitors* ErbB Receptors / metabolism Female Gefitinib / pharmacology* Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / enzymology Induced Pluripotent Stem Cells / pathology Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / enzymology Neoplastic Stem Cells / pathology Phosphoinositide-3 Kinase Inhibitors / pharmacology* Protein Kinase Inhibitors / pharmacology* Signal Transduction Tumor Burden / drug effects
IF 3.998
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001)