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Journals / Ege Tıp Dergisi / 2018 / Cilt: 57 - Sayı: 1

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

Hasan Onur ÇAĞLAR
SUNDE YILMAZ SÜSLÜER
CUMHUR GÜNDÜZ
Ayfer HAYDAROĞLU
Pages
36–45
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: In this study, it was observed that PD-0332991 leads to different expression profiles for cell cycle regulatory genes between BCSCs and breast cancer cells.

📌 3 Key Takeaways

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Objective & Hypothesis:Aim: Palbociclib (PD-0332991) is an inhibitor for cyclin-dependent kinase 4/6 complex and exhibits more activity in luminal ER+ breast cancer.
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Key Findings & Data:However, sensitivity of breast cancer stem cells (BCSCs) to PD-0332991 treatment and expression patterns of cell cycle regulatory genes after PD-0332991 treatment in BCSCs are still unclear.
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Conclusion & Impact:Conclusion: In this study, it was observed that PD-0332991 leads to different expression profiles for cell cycle regulatory genes between BCSCs and breast cancer cells.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Aim: Palbociclib (PD-0332991) is an inhibitor for cyclin-dependent kinase 4/6 complex and exhibits more activity in luminal ER+ breast cancer. However, sensitivity of breast cancer stem cells (BCSCs) to PD-0332991 treatment and expression patterns of cell cycle regulatory genes after PD-0332991 treatment in BCSCs are still unclear. This study aims to determine response of BCSCs to PD-0332991 treatment. Materials and Methods: An experimental in vitro study was designed on breast cancer cell lines. MCF-7 and BCSCs cell lines were used in this study. Water soluble tetrazolium salt-1 (WST-1) test was used for the cytotoxicity assay. Cell cycle distribution pattern and apoptosis were examined with flow cytometry according to IC50 values at 48th h. Real-Time PCR was used to detect expression profiles of CDKN1A, CHEK1, CDKN2A, CDC25A, and CCND1 genes. Results: PD-0332991 decreased cell proliferation in both cell lines. G0/G1 arrest was detected for both cell lines. There was no apoptotic effect of PD-0332991 on MCF-7 cells and BCSCs. In MCF-7 cells, expression levels of CDKN1A, CDKN2A, and CCND1 genes were increased as 3.11, 3.21, and 1.05 folds, respectively. Expression levels of CHEK1 and CDC25A genes were decreased as 4.75 and 3.73 folds, respectively. In BCSCs, expression levels of CDKN1A, CHEK1, CDKN2A, and CCND1 were decreased as 1.15, 2.01, 1.32, and 1.68 folds, respectively. No expression of CDC25A gene was found in BCSCs group. Conclusion: In this study, it was observed that PD-0332991 leads to different expression profiles for cell cycle regulatory genes between BCSCs and breast cancer cells.

Özet

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 RealTime PCR kullanıldıBulgular: 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.

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Cite This Article

ÇAĞLAR, H. O., SÜSLÜER, S. Y., GÜNDÜZ, C., HAYDAROĞLU, A. (2018). Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells. Ege Tıp Dergisi, Cilt: 57 - Sayı: 1, 36–45. https://ajindex.com/articles/222700

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