Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells

Hasan Onur Çağlar; Sunde Yılmaz Süslüer; Cumhur Gündüz; Ayfer Haydaroğlu

doi:10.19161/etd.414615

TR EN

Meme kanseri kanser kök hücrelerinde PD-0332991 uygulanmasının hücre döngüsü düzenleyici genler üzerine etkisi

Öz

Amaç: Palbociclib (PD-0332991) siklin bağımlı kinaz 4/6 kompleksi için bir inhibitördür ve luminal ER+ meme kanserlerinde daha fazla aktivite sergilemektedir. Ancak, meme kanseri kök hücrelerinin (MKKH) PD-0332991 uygulamasına olan hassasiyeti ve hücre döngüsü düzenleyici genleri üzerine PD-0332991’in etkisi MKKH’leri için açıklığa kavuşmamıştır. Bu çalışma, MKKH’lerinin PD-0332991 uygulamasına olan yanıtın belirlenmesini amaçlamaktadır.

Gereç ve Yöntem: Meme kanseri hücre hatları üzerinde deneysel bir in vitro çalışma tasarlanmıştır. Bu çalışmada, MCF-7 ve MKKH hücre hatları kullanıldı. Suda çözünür tetrazolyum tuzu-1 (WST-1) testi sitotoksisite deneyi için kullanıldı. Hücre döngüsü dağılımı ve apoptosis, 48. saat IC50 değerlerine göre flow sitometri ile incelendi. CDKN1A, CHEK1, CDKN2A, CDC25A ve CCND1 genlerinin ifade profillerinin belirlenmesinde Real-Time PCR kullanıldı.

Bulgular: Her iki hücre hattında, PD-0332991 hücre proliferasyonunu azalttı. Her iki hücre hattı için G0/G1 tutuklanması belirlendi. PD-0332991’in apoptotik etkisi MCF-7 ve MKKH hücrelerinde bulunmadı. MCF-7 hücrelerinde, CDKN1A, CDKN2A ve CCND1 ifade düzeyleri sırasıyla 3,11; 3,21 ve 1,05 kat arttı. CHEK1 ve CDC25A ifade düzeyleri sırasıyla 4,75 ve 3,73 kat azaldı. MKKH’lerinde CDKN1A, CHEK1, CDKN2A ve CCND1 ifade düzeleri sırasıyla 1,15; 2,01; 1,32 ve 1,68 kat azaldı. MKKH’lerinde, CDC25A geni ifadesi bulunmadı.

Sonuç: Bu çalışmada, MKKH ve meme kanseri hücreleri arasında PD-0332991’in hücre döngüsü düzenleyici genler için farklı ifade profillerine neden olduğu gözlenmiştir.

Anahtar Kelimeler

PD-0332991,meme tümörleri,neoplastik kök hücreler,G1 hücre döngüsü bloğu,hücre döngüsü.

References

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Details

Primary Language

English

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Hasan Onur Çağlar ^*
0000-0002-3637-4755
Türkiye

Sunde Yılmaz Süslüer
0000-0002-0535-150X
Türkiye

Cumhur Gündüz
0000-0002-6593-3237
Türkiye

Ayfer Haydaroğlu
0000-0001-5709-0981
Türkiye

Publication Date

March 1, 2018

Submission Date

August 22, 2016

Acceptance Date

February 28, 2018

Published in Issue

Year 1970 Volume: 57 Number: 1

DOI

https://doi.org/10.19161/etd.414615

IZ

https://izlik.org/JA77FH62RB

Cite

RIS / Bibtex

Vancouver

1.Hasan Onur Çağlar, Sunde Yılmaz Süslüer, Cumhur Gündüz, Ayfer Haydaroğlu. Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells. EJM. 2018 Mar. 1;57(1):36-45. doi:10.19161/etd.414615

Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells

Meme kanseri kanser kök hücrelerinde PD-0332991 uygulanmasının hücre döngüsü düzenleyici genler üzerine etkisi

Öz

Anahtar Kelimeler