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

Hale Guler Kara; Eda Doğan; Vildan Bozok; Şerif Şentürk; Buket Kosova

Makale detayları

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

Yazarlar:

Hale Guler Kara | Eda Doğan | Vildan Bozok | Şerif Şentürk | Buket Kosova

Yayıncı:

Mersin University

Ana Başlıklar:

Halk Sağlığı (Diğer)

Dergi:

Mersin Üniversitesi Sağlık Bilimleri Dergisi Vol.18 Issue 2, pp.183-193

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356040

pISSN:

1308-0830

Anahtar kelimeler:

Özet:

 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.

 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.

 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.

 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.

Makale detayları

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

Yazarlar:

Hale Guler Kara | Eda Doğan | Vildan Bozok | Şerif Şentürk | Buket Kosova

Yayıncı:

Mersin University

Ana Başlıklar:

Halk Sağlığı (Diğer)

Dergi:

Mersin Üniversitesi Sağlık Bilimleri Dergisi Vol.18 Issue 2, pp.183-193

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356040

pISSN:

1308-0830

Ovarian cancer

cisplatin resistance

VPS28

CRISPR-Cas9Over kanseri

cisplatin direnci

VPS28

CRISPR-Cas9

Sayı

Makale detayları

Yazarlar: Hale Guler Kara | Eda Doğan | Vildan Bozok | Şerif Şentürk | Buket Kosova

Yayıncı: Mersin University

Ana Başlıklar: Halk Sağlığı (Diğer)

Dergi: Mersin Üniversitesi Sağlık Bilimleri Dergisi Vol.18 Issue 2, pp.183-193

Belge Tipi: Makale

Yayın Tarihi: 8/2025

Belge Dili: Türkçe

Document ID (Org No.): 2001356040

pISSN: 1308-0830

Sayı

Yazarlar:

Hale Guler Kara | Eda Doğan | Vildan Bozok | Şerif Şentürk | Buket Kosova

Yayıncı:

Mersin University

Ana Başlıklar:

Halk Sağlığı (Diğer)

Dergi:

Mersin Üniversitesi Sağlık Bilimleri Dergisi Vol.18 Issue 2, pp.183-193

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356040

pISSN:

1308-0830