1. The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells.
- Author
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Xu Y, Afify SM, Du J, Liu B, Hassan G, Wang Q, Li H, Liu Y, Fu X, Zhu Z, Chen L, and Seno M
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Cell Self Renewal drug effects, ErbB Receptors metabolism, Female, Induced Pluripotent Stem Cells enzymology, Induced Pluripotent Stem Cells pathology, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neoplastic Stem Cells enzymology, Neoplastic Stem Cells pathology, Signal Transduction, Tumor Burden drug effects, Class Ib Phosphatidylinositol 3-Kinase metabolism, ErbB Receptors antagonists & inhibitors, Gefitinib pharmacology, Induced Pluripotent Stem Cells drug effects, Neoplastic Stem Cells drug effects, Phosphoinositide-3 Kinase Inhibitors pharmacology, Protein Kinase Inhibitors pharmacology
- 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., (© 2022. The Author(s).)
- Published
- 2022
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