Öz
Objectives: Thymoquinone a bioactive component extracted from the seeds of Nigella sativa, has been proved to have antiinflammatory, antioxidant properties anti antitumor efficiency against breast, prostate, bladder, and renal cell cancer. We aimed to investigate the synergistic cytotoxic and apoptotic effects of thymoquinone in combination with nivolumab, an immuno-control inhibitor, and its mechanism in renal cell cancer models. Materials and Methods: In vitro studies: Caki-1 and Renca renal cancer cell lines with mononuclear cells were cocultured and thymoquinone and nivolumab effect were analyzed by MTT and Annexin V + PI. In vivo studies: Renal cell cancer model was provided by subcutaneous injection of RENCA cells to C57BL/6, male, 8 weeks old mice in four groups. Control group, thymoquinone (1,4,7,14days,20mg/kgIP), nivolumab administered (1,6,13days10mg/ kgIP), thymoquinone and nivolumab. Seven animals was randomized in each experimental group. Apoptosis, necrosis, CD4,CD8,C20,CD34,CD31,VEGF-A by immunohistochemistry, FGFR-1,PDGFRbeta,VEGFR-2,c-kit,RET,c-Met,AXL,Flt-3,TIE2, ICAM-1,VCAM-1 and E-selectin mRNA levels by quantitative real-time- PCR were evaluated on tumor tissue. Liver, kidney, brain, lung and heart tissues was evaluated for side effects. Plasma biochemistry tests were performed. Statistical analysis was be performed with Mann-Whitney U test with p <0.05 value. Results: Thymoquinone showed antitumor effect in vitro and in vivo. It also showed increase in immune cell death of nivolumab. Tumor tissue showed prominent necrosis or complete response to therapy in combination group. Conclusions: We conclude that thymoquinone has antitumor effect on renal cell carcinoma and increases the effect of nivolumab immune, cell death effects. Besides, it does not have side effect on other organs whether alone or in combination.
Anahtar Kelimeler
Renal Cell Cancer Thymoquinone Immune Check Point Inhibitors
Destekleyen Kurum
Dokuz Eylul University Scientific Project Comission
Proje Numarası
2020.KB.SAG.065
Kaynakça
- Curtius K, Wright NA, Graham TA. Evolution of Premalignant Disease. Cold Spring Harb Perspect Med. 2017;7(12)
Öz
Objectives: Thymoquinone a bioactive component extracted from the seeds of Nigella sativa, has been proved to have antiinflammatory, antioxidant
properties anti antitumor efficiency against breast, prostate, bladder, and renal cell cancer. We aimed to investigate the synergistic cytotoxic and apoptotic
effects of thymoquinone in combination with nivolumab, an immuno-control inhibitor, and its mechanism in renal cell cancer models.
Materials and Methods: In vitro studies: Caki-1 and Renca renal cancer cell lines with mononuclear cells were cocultured and thymoquinone and
nivolumab effect were analyzed by MTT and Annexin V + PI. In vivo studies: Renal cell cancer model was provided by subcutaneous injection of RENCA
cells to C57BL/6, male, 8 weeks old mice in four groups. Control group, thymoquinone (1,4,7,14days,20mg/kgIP), nivolumab administered (1,6,13days10mg/
kgIP), thymoquinone and nivolumab. Seven animals was randomized in each experimental group. Apoptosis, necrosis, CD4,CD8,C20,CD34,CD31,VEGF-A by
immunohistochemistry, FGFR-1,PDGFRbeta,VEGFR-2,c-kit,RET,c-Met,AXL,Flt-3,TIE2, ICAM-1,VCAM-1 and E-selectin mRNA levels by quantitative real-time-
PCR were evaluated on tumor tissue. Liver, kidney, brain, lung and heart tissues was evaluated for side effects. Plasma biochemistry tests were performed.
Statistical analysis was be performed with Mann-Whitney U test with p <0.05 value.
Results: Thymoquinone showed antitumor effect in vitro and in vivo. It also showed increase in immune cell death of nivolumab. Tumor tissue showed
prominent necrosis or complete response to therapy in combination group.
Conclusions: We conclude that thymoquinone has antitumor effect on renal cell carcinoma and increases the effect of nivolumab immune, cell death
effects. Besides, it does not have side effect on other organs whether alone or in combination.
Anahtar Kelimeler
Renal Cell Cancer Thymoquinone Immune Check Point Inhibitors
Proje Numarası
2020.KB.SAG.065
Kaynakça
- Curtius K, Wright NA, Graham TA. Evolution of Premalignant Disease. Cold Spring Harb Perspect Med. 2017;7(12)
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Toplantı Özeti |
| Yazarlar | |
| Proje Numarası | 2020.KB.SAG.065 |
| Yayımlanma Tarihi | 9 Ağustos 2022 |
| Gönderilme Tarihi | 5 Temmuz 2022 |
| Yayımlandığı Sayı | Yıl 2022 |