Deneysel Renal Kanser Modelinde Thymoquinone ve Nivolumab’ın Potansiyel Sinerjistik Etkisi

Abstract

Amaç: Thymoquinone ve Nivolumab kombinasyonunun deneysel böbrek hücre kanseri modelleri üzerindeki etkilerini araştırdık. Thymoquinone, Nigella sativa tohumlarından çıkarılan biyolojik olarak aktif bir bileşiktir, Thymoquinone 'nun çeşitli kanserlere karşı anti-inflamatuar, antioksidan ve anti-tümör özellikleri vardır. Gereç ve Yöntem: Thymoquinone ve Nivolumab’ın etkisi, Renca hücre hattı kullanılarak 3-(4,5-dimetiltiyazol-.2-yl)-2,5 difeniltetrazolyum-bromür ve Annexin-V + propidyum iyodür testleri ile analiz edildi. Renca hücreleri 8 haftalık erkek C57BL/6 farelerine subkutan olarak enjekte edildi. Gruplar kontrol, Thymoquinone, Nivolumab, Thymoquinone +Nivolumab olarak tasarlandı. Tümör dokuları, p<0,05 anlamlılık düzeyinde apoptoz/nekroz oranları, immünmarkerlerin ekspresyonu ve ribonükleik asit ekspresyonu açısından analiz edildi. Bulgular: Bulgularımız, Thymoquinone 'nun hem in vitro hem de in vivo olarak anti-tümör etkileri olduğunu gösterdi. Nivolumab ile kombinasyon tedavisi, immün aracılı tümör hücre ölümü artışına yol açarak tümör dokusunda önemli nekroz veya tedaviye tam yanıt ile sonuçlandı. Sonuç: Thymoquinone'un böbrek hücreli karsinom üzerinde anti-tümör etkisi olduğu ve Nivolumab'ın bağışıklık hücresi apoptozunu artırdığı sonucuna varılmıştır. Ayrıca, tek başına veya kombinasyon halinde kullanıldığında diğer organlarda yan etkisi yoktur. Anahtar Kelimeler: Bağışıklık kontrol noktası inhibitörleri, böbrek hücreli kanseri, thymoquinone.

Keywords

• Böbrek Hücreli Kanseri
• Timoquinon
• Bağışıklık Kontrol Noktası İnhibitörleri

Project Number

2020.KB.SAG.047.

Potential Therapeutic Synergy of Thymoquinone and Nivolumab in Experimental Models of Renal Cancer

Abstract

Objective: We investigated the effects of Thymoquinone in combination with Nivolumab on experimental renal cell cancer models. Thymoquinone, a bioactive component extracted from Nigella sativa seeds, exhibits anti inflammatory, antioxidant, and anti-tumor properties against various cancers. Material and Methods: The effects of Thymoquinone and Nivolumab were analyzed using the Renca cell line with 3 (4,5-dimetiltiyazol-. 2-yl)-2.5- difeniltetrazolium-bromure and Annexin V + propidium iodure assays. Renca cells were subcutaneously injected into 8-week-old male C57BL/6 mice. Groups were designed as control, Thymoquinone, Nivolumab, Thymoquinone+Nivolumab. Tumor tissues were analyzed for apoptosis/necrosis rates, expression of immunomarkers, and ribonucleic acid expression at a significance level of p<0.05. Results: The results showed that Thymoquinone had anti tumor effects both in vitro and in vivo. The combination treatment with Nivolumab led to an increase in immune-mediated tumor cell death, resulting in significant necrosis or complete response to therapy in the tumor tissue. Conclusion: Thymoquinone has been found to have an anti tumor effect on renal cell carcinoma, and Nivolumab has been shown to enhance the impact of immune cell apoptosis. Additionally, there are no side effects on other organs when used alone or in combination. Keywords: Immune checkpoint inhibitors, renal cell cancer, thymoquinone.

Keywords

• Renal Cell Cancer
• Thymoquinone
• Immune Checkpoint Inhibitors

Supporting Institution

This study was supported by Dokuz Eylul University Scientific Research Council by project number 2020.KB.SAG.047.

Project Number

2020.KB.SAG.047.

Ethical Statement

The study was conducted in accordance with the ethical principles of the 1964 Helsinki Declaration and complied with these standards. All of the experimental procedures involving animals were conducted in accordance with the Experimental Animal Care Regulations of Dokuz Eylul University, Turkey and approved by the Ethics Committee of the Dokuz Eylul University, Turkey with an approved number 22/2017.

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