Kalsitriol’ün İnsan Ovaryum Kanser Hücrelerine Etkisinin Araştırılması

Year 2024, , 22 - 28, 29.04.2024

Bahar Kartal , Ebru Alimoğulları

https://doi.org/10.46332/aemj.1228216

Abstract

Amaç: Over kanseri jinekolojik malignitelerden ölümlerin önde gelen nedenlerindendir. Kadınlarda kansere bağlı ölümlerde beşinci sırada ye almaktadır. D Vitaminin aktif formu olan kalsitirol, vitamin D reseptörüne (VDR) bağlanarak fonksiyon göstermektedir. Kalsitriol, proliferasyon, apoptoz, diferansiasyon, inflamasyon, invazyon, anjiyogenez ve metastaz ile ilgili çoklu sinyal yollarını düzenleyerek kanser gelişimini ve büyümesini etkileme potansiyeline sahiptir. Kolon, meme ve prostat kanseri büyümesini sağlayan spesifik sinyal yollarının kalsitriol ile düzenlemesi incelendiğinde kalsitriolün birçok farklı kanser türünde kanser hücreleri üzerinde geniş bir etkiye sahip olduğu görülmüştür. Çalışmamızın amacı kalsitriolün ovaryum kanser hücrelerine karşı etkisini araştırmaktır.
Araçlar ve Yöntem: Çalışmamızda MDAH-2774 insan ovaryum kanseri hücre hattı kullanılmıştır. Hücreler farklı dozlarda kalsitriole 24 ve 48 saat maruz bırakıldıktan sonra MTT testi ve kantitatif gerçek zamanlı -PCR yöntemi uygulanmıştır.
Bulgular: MTT testi sonucunda, kalsitirolün ovaryum kanser hücrelerinin canlılığını azalttığı tespit edildi. Kalsitriol uygulanan grupta kontrol grubuna kıyasla VDR ve p53 gen ekspresyonlarında artış saptandı. Bunlara ek olarak, kalsitriol uygulamasının proapoptotik belirteç Bax'ın gen expresyonunda artışa ve anti-apoptotik Bcl-2 ekspresyonunda azalmaya neden olduğu tespit edildi.
Sonuç: Sonuç olarak kalsitriol tedavisinin, ovaryum kanser hücrelerinin proliferasyonunu azalttığı ve apoptozu indüklediği saptanmış olup, kasitriolün tek başına veya kemoterapi ilaçlarıyla kombinasyon halinde kullanılmasının ovaryum kanser tedavilerinde potansiyel bir rolü olduğu düşünülmektedir.

Keywords

apoptoz, kalsitriol, mtt analizi, ovaryum kanseri, qrt-pcr

The Investigation of the Effects of Calcitriol on Human Ovarian Carcinoma Cells

Abstract

Purpose: Ovarian cancer is the fifth leading cause of cancer death in women, leading cause of death from gynecologic malignancies, and the second most commonly diagnosed gynecologic malignancy, however the underlying pathophysiology is not clearly understood. Calcitriol, the active form of vitamin D serves its activity by binding to the vitamin D receptor (VDR). Calcitriol regulates multiple signaling pathways such as proliferation, apoptosis, differentiation, inflammation, invasion, angiogenesis and metastasis. It has been found to have a broad effect on several cancer types such as colon, breast and prostate cancer. Therefore, the study aimed to investigate the effects of calcitriol on human ovarian cancer cells.

Material and Methods: The human MDAH-2774 ovarian carcinoma cells were exposed to different dose ranges of calcitriol for 24 and 48 hours. Cultured cells were evaluated in terms of MTT assay and quantitative- Real time-PCR.

Results: As evidenced by the MTT assay, calcitriol treatment resulted in the reduction of cell viability in human MDAH-2774 cells. The gene expressions of VDR and p53 were increased with the calcitriol treatment compared to control. Additionally the gene expression of proapoptotic marker Bax increased and the anti-apoptotic marker Bcl-2 decreased with the presence of the calcitriol.

Conclusion: In conclusion calcitriol treatment decreased cell proliferation and induced apoptosis in ovarian cancer cells, therefore we can suggest that calcitriol, either by itself or in combination with chemotherapy drugs, may be effective in treating ovarian cancer.

Keywords

apoptosis, calcitriol, mtt assay, ovarian cancer, qrt-pcr

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