Combination therapy using TGF-β1 and STI-571 can induce apoptosis in BCR-ABL oncogene-expressing cells

Abstract: The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-β1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-β1 on K562 cells was studied in the present research. Results revealed that the TGF-β1 cell signaling pathway, which is activated in K562 cells treated with TGF-β1, activates collective cell signaling pathways involved in survival and apoptosis. It is noteworthy that treating K562 cells with STI-571 triggered apoptotic pathways, accompanied by a reduction in proteins such as Bcl-xL, Bcl-2, p-AKT, p-Stat5, p-FOXO3, and Mcl-1 and an increase in the pro-apoptotic proteins PARP cleavage, and p27, leading to an increase in sub-G1 phase-arrested and Annexin-positive cells. Interestingly, the proliferation behavior of TGF-β1-induced cells was changed with the combination therapy, and STI-571-induced apoptosis was also prompted by this combination. Thus, combination treatment appears to promote sub-G1 cell cycle arrest compared to individually treated cells. Furthermore, it strongly triggered apoptotic signaling. In conclusion, TGF-β1 did not negatively impact the effect of STI-571, based on positive annexin cells, and AKT protein phosphorylation remains effective in apoptosis.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Combination therapy using TGF-β1 and STI-571 can induce apoptosis in BCR-ABL oncogene-expressing cells ; volume:12 ; number:1 ; year:2021 ; pages:144-155 ; extent:12
Biomolecular concepts ; 12, Heft 1 (2021), 144-155 (gesamt 12)

Urheber
Bakhshayesh, Masoome
Gohari, Ladan Hosseini
Barati, Mahmood
Safa, Majid

DOI
10.1515/bmc-2021-0016
URN
urn:nbn:de:101:1-2409241659212.974657131939
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:21 MESZ

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Beteiligte

  • Bakhshayesh, Masoome
  • Gohari, Ladan Hosseini
  • Barati, Mahmood
  • Safa, Majid

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