Muscarinic Receptors as Targets for Metronomic Therapy in Ovarian Cancer

Fatma Söylemez; Çağatay Han Türkseven

Makale detayları

Muscarinic Receptors as Targets for Metronomic Therapy in Ovarian Cancer

Yazarlar:

Fatma Söylemez | Çağatay Han Türkseven

Yayıncı:

Duzce University

Ana Başlıklar:

Cancer Cell Biology

Dergi:

Duzce Medical Journal Vol.25 Issue 3, pp.225-230

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001297975

pISSN:

1307-671X

Anahtar kelimeler:

Özet:

 Aim: In this study, the effects of muscarinic acetylcholine receptor mAChR agonist carbachol on the proliferation of cisplatin-resistant A2780cis and cisplatin-free SKOV-3 ovarian cancer cell line were for the first time investigated to further evaluate the potential therapeutic effect of metronomic chemotherapy. Material and Methods: The inhibitory effect of carbachol on cell proliferation was detected using the xCELLigence Real-Time Cell Analyzer RTCA dual plate DP system. A preliminary study was conducted to determine the dose of carbachol 100 µM, cisplatin 1 µM, and two combination studies were carried out with 100 µM carbachol  cisplatin 1 µM and 100 µM carbachol  10 µM atropine, over cancer cells without drugs was used as the control group. The cell proliferation curve was monitored for 96 hours. The cell index value of inhibition in cell proliferation was automatically measured every hour for each well using RTCA 1.2.1 software. Results: Co-administration of carbachol with cisplatin caused a decrease in cell number in both A2780cis and SKOV-3 cell lines in a time-dependent manner p0.001. Substantial cell death was observed in both cisplatin-resistant A2780cis and cisplatin-free SKOV-3 cell lines within 24 hours after carbachol with cisplatin application and this continued at the 96th hour. Conclusion: The findings of this study confirm the notion that mAChRs can be considered as therapeutic targets for metronomic therapy in ovarian cancer, as well as the usefulness of a muscarinic agonist as a repositioning drug in the treatment of such tumors.

 Aim: In this study, the effects of muscarinic acetylcholine receptor mAChR agonist carbachol on the proliferation of cisplatin-resistant A2780cis and cisplatin-free SKOV-3 ovarian cancer cell line were for the first time investigated to further evaluate the potential therapeutic effect of metronomic chemotherapy. Material and Methods: The inhibitory effect of carbachol on cell proliferation was detected using the xCELLigence Real-Time Cell Analyzer RTCA dual plate DP system. A preliminary study was conducted to determine the dose of carbachol 100 µM, cisplatin 1 µM, and two combination studies were carried out with 100 µM carbachol  cisplatin 1 µM and 100 µM carbachol  10 µM atropine, over cancer cells without drugs was used as the control group. The cell proliferation curve was monitored for 96 hours. The cell index value of inhibition in cell proliferation was automatically measured every hour for each well using RTCA 1.2.1 software. Results: Co-administration of carbachol with cisplatin caused a decrease in cell number in both A2780cis and SKOV-3 cell lines in a time-dependent manner p0.001. Substantial cell death was observed in both cisplatin-resistant A2780cis and cisplatin-free SKOV-3 cell lines within 24 hours after carbachol with cisplatin application and this continued at the 96th hour. Conclusion: The findings of this study confirm the notion that mAChRs can be considered as therapeutic targets for metronomic therapy in ovarian cancer, as well as the usefulness of a muscarinic agonist as a repositioning drug in the treatment of such tumors.

 Aim: In this study, the effects of muscarinic acetylcholine receptor mAChR agonist carbachol on the proliferation of cisplatin-resistant A2780cis and cisplatin-free SKOV-3 ovarian cancer cell line were for the first time investigated to further evaluate the potential therapeutic effect of metronomic chemotherapy. Material and Methods: The inhibitory effect of carbachol on cell proliferation was detected using the xCELLigence Real-Time Cell Analyzer RTCA dual plate DP system. A preliminary study was conducted to determine the dose of carbachol 100 µM, cisplatin 1 µM, and two combination studies were carried out with 100 µM carbachol  cisplatin 1 µM and 100 µM carbachol  10 µM atropine, over cancer cells without drugs was used as the control group. The cell proliferation curve was monitored for 96 hours. The cell index value of inhibition in cell proliferation was automatically measured every hour for each well using RTCA 1.2.1 software. Results: Co-administration of carbachol with cisplatin caused a decrease in cell number in both A2780cis and SKOV-3 cell lines in a time-dependent manner p0.001. Substantial cell death was observed in both cisplatin-resistant A2780cis and cisplatin-free SKOV-3 cell lines within 24 hours after carbachol with cisplatin application and this continued at the 96th hour. Conclusion: The findings of this study confirm the notion that mAChRs can be considered as therapeutic targets for metronomic therapy in ovarian cancer, as well as the usefulness of a muscarinic agonist as a repositioning drug in the treatment of such tumors.

 Amaç: Bu çalışmada, muskarinik asetilkolin reseptörü mAChR agonisti karbakolun, sisplatine dirençli A2780cis ve sisplatine dirençsiz SKOV-3 yumurtalık kanseri hücre hatlarının proliferasyonu üzerindeki etkileri, metronomik kemoterapinin potansiyel terapötik etkisini daha ileri düzeyde değerlendirmek üzere ilk kez araştırıldı. Gereç ve Yöntemler: Karbakolün hücre proliferasyonu üzerindeki inhibitör etkisi, xCELLigence Real-Time Cell Analyzer RTCA dual plate DP sistemi kullanılarak tespit edildi. 100 µM karbakol ve 1 µM sisplatin dozunu belirlemek için bir ön çalışma yapıldı ve 100 µM karbakol  1 µM sisplatin ve 100 µM karbakol  10 µM atropin olmak üzere iki kombinasyon çalışması yapıldı, ilaçsız yumurtalık kanser hücreleri ise kontrol grubu olarak kullanıldı. Hücre proliferasyon eğrisi 96 saat izlendi. Hücre proliferasyonundaki inhibisyonun hücre indeksi değeri, RTCA 1.2.1 yazılımı ile her kuyu için her saat otomatik olarak ölçüldü. Bulgular: Karbakolun sisplatin ile birlikte uygulanması hem A2780cis hem de SKOV-3 hücre hatlarında zamana bağlı olarak hücre sayısında azalmaya neden olmuştur p0.001. Sisplatin ile karbakol uygulamasından sonraki 24 saat içinde sisplatine dirençli A2780cis ve sisplatine dirençsiz SKOV-3 her iki hücre hattında da önemli düzeyde hücre ölümü gözlenmiş ve bu durum 96. saatte de devam etmiştir p0.001. Sonuç: Bu çalışmanın bulguları, mAChRlerin yumurtalık kanserinde metronomik tedavi için terapötik hedefler olarak kabul edilebileceği fikrini ve ayrıca bu tür tümörlerin tedavisinde bir muskarinik agonistin bir yeniden konumlandırma ilacı olarak kullanışlılığını doğrulamaktadır.

Makale detayları

Muscarinic Receptors as Targets for Metronomic Therapy in Ovarian Cancer

Yazarlar:

Fatma Söylemez | Çağatay Han Türkseven

Yayıncı:

Duzce University

Ana Başlıklar:

Cancer Cell Biology

Dergi:

Duzce Medical Journal Vol.25 Issue 3, pp.225-230

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001297975

pISSN:

1307-671X

Ovary cancer;

mAChR;

Carbachol;

SKOV-3;

A2780CIS;

cisplatinYumurtalık kanseri;

mAChR;

Karbakol;

SKOV-3;

A2780CIS;

Sisplatin

Sayı

Makale detayları

Yazarlar: Fatma Söylemez | Çağatay Han Türkseven

Yayıncı: Duzce University

Ana Başlıklar: Cancer Cell Biology

Dergi: Duzce Medical Journal Vol.25 Issue 3, pp.225-230

Belge Tipi: Makale

Yayın Tarihi: 12/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001297975

pISSN: 1307-671X

Sayı

Yazarlar:

Fatma Söylemez | Çağatay Han Türkseven

Yayıncı:

Duzce University

Ana Başlıklar:

Cancer Cell Biology

Dergi:

Duzce Medical Journal Vol.25 Issue 3, pp.225-230

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001297975

pISSN:

1307-671X