| RRC ID |
74515
|
| 著者 |
Xu Y, Afify SM, Du J, Liu B, Hassan G, Wang Q, Li H, Liu Y, Fu X, Zhu Z, Chen L, Seno M.
|
| タイトル |
The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells.
|
| ジャーナル |
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.
|
| 巻・号 |
12(1)
|
| ページ |
347
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
iPS-MEF-Ng-20D-17(APS0001) |
