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Dergiler / Mersin Üniversitesi Sağlık Bilimleri Dergisi / 2026 / Cilt: 18 Sayı: 2

Kemoterapi dirençli over kanseri hücrelerinde VPS28 geninin CRISPR-Cas9 yöntemi ile susturulmasının cisplatin yanıtı üzerine etkileri

Effects of CRISPR-Cas9 silencing of VPS28 gene on cisplatin response in chemotherapy-resistant ovarian cancer cells

Hale Guler Kara(HARRAN ÜNİVERSİTESİ)0000-0002-4304-3727
Eda Doğan0000-0003-0192-1429
Vildan Bozok(Ege Üniversitesi)0000-0003-3915-6363
Şerif Şentürk(DOKUZ EYLÜL ÜNİVERSİTESİ, İZMİR ULUSLARARASI BİYOTIP VE GENOM ENSTİTÜSÜ)0000-0003-3963-2294
Buket Kosova(EGE ÜNİVERSİTESİ, EGE TIP FAKÜLTESİ)0000-0003-3636-6082
Sayfa
183–193
Yayın Tarihi
2025-08-15
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Bulgular: Yapılan fonksiyonel analizler sonucunda, cisplatin dirençli over kanseri hücrelerinde VPS28 geninin susturulması ile cisplatin duyarlılığının arttığı, apoptozun indüklendiği ve hücre döngüsü S evresinde mitotik katastrofa neden olduğu belirlenmiştir.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Amaç: Günümüzde yumurtalık (over) kanseri kadınlarda halen yaygın olarak görülmekte ve jinekolojik kansere bağlı ölüm nedenlerinin başında gelmektedir.
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Temel Bulgular & Veri:Bu çalışmada multiveziküler cisim biyogenezinde etkin ESCRT-I kompleks bileşeni VPS28 geninin, over kanseri cisplatin direncindeki olası rolünün belirlenmesi amaçlanmıştır.
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Sonuç & Katkı:Bulgular: Yapılan fonksiyonel analizler sonucunda, cisplatin dirençli over kanseri hücrelerinde VPS28 geninin susturulması ile cisplatin duyarlılığının arttığı, apoptozun indüklendiği ve hücre döngüsü S evresinde mitotik katastrofa neden olduğu belirlenmiştir.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Over kanseri · cisplatin direnci · VPS28

Özet

Amaç: Günümüzde yumurtalık (over) kanseri kadınlarda halen yaygın olarak görülmekte ve jinekolojik kansere bağlı ölüm nedenlerinin başında gelmektedir. Tedavisinde sıklıkla kemoterapötik bir ajan olan cisplatin kullanılmakla birlikte, zamanla hastalarda cisplatine karşı direnç gelişmekte ve direnç gelişiminde genetik faktörlerin sorumlu olduğu bilinmektedir. Bu çalışmada multiveziküler cisim biyogenezinde etkin ESCRT-I kompleks bileşeni VPS28 geninin, over kanseri cisplatin direncindeki olası rolünün belirlenmesi amaçlanmıştır. Yöntem: Cisplatin dirençli A2780 over kanseri hücre serisinde VPS28 geni CRISPR-Cas9 yöntemiyle susturulduktan sonra proliferasyon, cisplatin yanıtı, apoptoz ve hücre döngüsü üzerine etkileri araştırılmıştır. Bulgular: Yapılan fonksiyonel analizler sonucunda, cisplatin dirençli over kanseri hücrelerinde VPS28 geninin susturulması ile cisplatin duyarlılığının arttığı, apoptozun indüklendiği ve hücre döngüsü S evresinde mitotik katastrofa neden olduğu belirlenmiştir. Sonuç: VPS28 geninin A2780 over kanseri hücrelerindeki kazanılmış cisplatin direncinde etkili olduğu ve susturulmasının, tedavisinde kullanılan cisplatin ile birlikte sinerjistik etki yarattığı gösterilmiştir.

Abstract

Aim: Today, ovarian cancer is still common in women and is the leading cause of deaths from gynecologic cancer. Although cisplatin, a chemotherapeutic agent, is frequently used in the treatment, resistance to cisplatin develops in patients over time and genetic factors are known to be responsible for the development of resistance. In this study, it was aimed to determine the possible role of the ESCRT-I complex component VPS28 gene, which is active in multivesicular body biogenesis, in ovarian cancer cisplatin resistance. Method: After silencing the VPS28 gene in cisplatin-resistant A2780 ovarian cancer cells using the CRISPR-Cas9 method, the effects on proliferation, cisplatin response, apoptosis and cell cycle were investigated. Results: Functional analyses revealed that VPS28 gene silencing in chemotherapy-resistant ovarian cancer increased cisplatin sensitivity, induced apoptosis, and caused mitotic catastrophe by arresting the cell cycle in the S phase. Conclusion: The VPS28 gene has been shown to be involved in acquired cisplatin resistance in A2780 ovarian cancer cells, and its silencing has a synergistic effect with the cisplatin used in treatment.

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Bu Makaleye Atıf Yap

Kara, H. G., Doğan, E., Bozok, V., Şentürk, Ş., Kosova, B. (2025). Kemoterapi dirençli over kanseri hücrelerinde VPS28 geninin CRISPR-Cas9 yöntemi ile susturulmasının cisplatin yanıtı üzerine etkileri. Mersin Üniversitesi Sağlık Bilimleri Dergisi, Cilt: 18 Sayı: 2, 183–193. https://doi.org/10.26559/mersinsbd.1609536

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