Aurora B kinase inhibition intensifies cisplatin cytotoxicity in MCF7 breast cancer cells

Ronahi Askan; Ramazan Gundogdu

doi:10.19161/etd.1417750

EN TR

Aurora B kinase inhibition intensifies cisplatin cytotoxicity in MCF7 breast cancer cells

Abstract

Aim: Cancer, a complex and multifaceted group of diseases, poses a formidable challenge to global health. Characterised by uncontrolled cell growth and proliferation, it manifests in diverse forms, each with unique biological traits. Understanding the complexity of cancer biology is essential for developing targeted therapeutic interventions. This research aimed to explore the impact of inhibiting Aurora B kinase with BI 831266 on the anticancer efficacy of cisplatin in MCF7 cells, contributing to our understanding of potential treatment strategies. Materials and Methods: Good Cell Culture Practices were conducted in this research, where MCF7 human breast cancer cells were used in order to assess the therapeutic potential of the BI 831266 and cisplatin combination. Regarding functional experiments, we employed in vitro cell proliferation assay, 2D clonogenic survival assay, 3D colony formation assay and wound-healing assay. To elucidate the molecular mechanism underlying the observed functional outcomes, SDS-PAGE and Western blotting experiments were additionally conducted. Results: Our findings uncovered a synergistic interaction between inhibiting Aurora B kinase and treating MCF7 cancer cells with cisplatin. The combined treatment significantly increased cisplatin's cytotoxicity, hindered cancer cell migration, and influenced apoptotic pathways, as evident from changes in key protein expressions. Conclusion: Our research emphasises the significance of targeting Aurora B kinase in order to enhance therapeutic responses of cisplatin in MCF7 breast cancer cells. The study contributes valuable insights into potential combination therapies, offering a more effective and targeted approach for treating breast cancer.

Keywords

Aurora B kinaz inhibisyonu MCF7 meme kanseri hücrelerinde sisplatin sitotoksisitesini yoğunlaştırır

Öz

Amaç: Karmaşık ve çok yönlü bir hastalık grubu olan kanser, küresel sağlık açısından zorlu bir sorun teşkil etmektedir. Kontrolsüz hücre büyümesi ve çoğalması ile karakterize edilen bu hastalık, her biri benzersiz biyolojik özelliklere sahip olan çeşitli formlarda kendini göstermektedir. Kanser biyolojisinin karmaşıklığının anlaşılması, hedefe yönelik terapötik müdahalelerin geliştirilmesi için önemlidir. Bu araştırma, Aurora B kinazın BI 831266 ile inhibe edilmesinin, MCF7 hücrelerinde sisplatinin anti-tümör etkinliği üzerindeki etkisini araştırmayı ve potansiyel tedavi stratejilerini anlamamıza katkıda bulunmayı amaçlamaktadır. Gereç ve Yöntem: BI 831266 ve sisplatin kombinasyonunun terapötik potansiyelini değerlendirmek amacıyla MCF7 insan meme kanseri hücrelerinin kullanıldığı bu araştırmada İyi Hücre Kültürü Uygulamaları gerçekleştirilmiştir. Fonksiyonel deneylerle ilgili olarak, in vitro hücre proliferasyon analizi, 2D klonojenik sağkalım analizi, 3D koloni formasyon analizi ve yara iyileşme analizi uygulandı. Gözlemlenen fonksiyonel sonuçların altında yatan moleküler mekanizmayı açıklamak için ayrıca SDS-PAGE ve Western blot deneyleri gerçekleştirildi. Bulgular: Bulgularımız, MCF7 kanser hücrelerinde Aurora B kinazın inhibe edilmesi ile sisplatin tedavisi arasında sinerjistik bir etkileşimi ortaya çıkardı. Kombinasyon tedavisinin, önemli protein ifadelerindeki değişikliklerden de anlaşılacağı üzere sisplatinin sitotoksisitesini önemli ölçüde arttırdığı, kanser hücresi göçünü engellediği ve apoptotik yolakları etkinleştirdiği belirlendi. Sonuç: Araştırmamız, MCF7 meme kanseri hücrelerinde sisplatinin terapötik yanıtını arttırmak için Aurora B kinaz aktivitesini hedeflemenin önemini vurgulamaktadır. Çalışmamız, meme kanseri tedavisinde daha etkili ve hedefe yönelik bir yaklaşım sunarak potansiyel kombinasyon tedavilerine değerli katkılar sağlamaktadır.

Anahtar Kelimeler

Destekleyen Kurum

Projemiz Bingöl Üniversitesi Bilimsel Araştırma Projeleri (BAP) Birimi tarafından desteklenmiştir.

Proje Numarası

The Scientific Research Projects Coordination Unit of Bingol University, BAP-SHMYO.2023.001

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Kanser Hücre Biyolojisi , Moleküler Hedefler

Bölüm

Araştırma Makalesi

Yazarlar

Ronahi Askan
0009-0002-8787-5397
Türkiye

Ramazan Gundogdu ^*
0000-0001-5230-2121
Türkiye

Yayımlanma Tarihi

9 Eylül 2024

Gönderilme Tarihi

10 Ocak 2024

Kabul Tarihi

29 Nisan 2024

Yayımlandığı Sayı

Yıl 1970 Cilt: 63 Sayı: 3

DOI

https://doi.org/10.19161/etd.1417750

IZ

https://izlik.org/JA77AT34PJ

Kaynak Göster

RIS / Bibtex

Vancouver

1.Ronahi Askan, Ramazan Gundogdu. Aurora B kinase inhibition intensifies cisplatin cytotoxicity in MCF7 breast cancer cells. ETD. 01 Eylül 2024;63(3):410-21. doi:10.19161/etd.1417750