Vitamin D’nin Hepatoselüler Karsinom Üzerindeki Etkisi

Year 2020, Volume 42, Issue 3, 301 - 310, 27.05.2020

Çağrı ÖNER Hatice İSAN Ranan Gülhan AKTAŞ Ertuğrul ÇOLAK

https://doi.org/10.20515/otd.584749

Abstract

Hepatoselüler karsinoma (HCC) dünya çapında görülme sıklığı açısından en çok görülen dördüncü kanser türüdür. Bu kanser türünün görülme nedenlerinin başında Tip II diyabet, obezite ve alkol kullanımı gelmektedir. Çalışmamızda, karaciğer hastalıklarında etkili olan, ancak hücresel mekanizmalar açısından etkileşimi henüz tam olarak belirlenemeyen vitamin D’nin hem ilaç formu hem de aktif formu olan 1,25-dihidroksivitaminin [1,25(OH)2D3] HepG2 hepatoselüler karsinom hücrelerinin karakteristik özelliklerinde oluşturduğu değişimlerin belirlenmesi amaçlanmıştır. HepG2 hücrelerine vitamin D’nin hem ilaç formu hem de 1,25(OH)2D3 formu ayrı ayrı uygulanarak en etkili konsantrasyonları ve saatleri belirlendi. Bu aşamadan sonra uygun konsantrasyon ve saatte uygulanan her iki maddenin HepG2 hücrelerinin proliferasyonu, adezyonu ve immunohistokimyasal olarak p53 miktarındaki etkileri belirlendi. Elde edilen verilere göre, 250 nM vitamin D’nin ilaç formu HepG2 hücrelerine uygulandıktan 96 saat; 250 nM 1,25(OH)2D3 uygulandıktan sonra 48 saat sonra kontrol grubuna göre istatistiksel olarak proliferasyonun en çok görüldüğü konsantrasyon ve saat olarak belirlendi. Hem vitamin D’nin ilaç hem de 1,25(OH)2D3 formu HepG2 hücrelerinin adezyonunu kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde azaldığı belirlendi (p<0.001). Optimal konsantrasyon ve saatte uygulanan her iki vitamin D formunun p53 miktarındaki değişimleri immunohistokimyasal olarak incelendiğinde, kontrol ve sham gruplarına göre azaldığı gözlendi. Hepatoselüler kanser hastalarında uygulanacağı zaman, vitamin D dozuna dikkat edilmesi ve sürekli kontrol altında olunması yönünde ön veri sağlamaktadır. Her ne kadar bazı karaciğer hastalıklarından korunmak için önemli bir vitamin olmasına rağmen; kanser hücrelerinde proliferasyonu arttırması, adezyonu azaltması ve bir tümör baskılayıcı olan p53 miktarını azaltması konu üzerinde soru işaretleri yaratmaktadır. Vitamin D’nin hepatoselüler hastalar üzerinde uygulanması konusunda farklı bir bakış açısı yaratan sonuçlarımız, ilerleyen dönemlerde konu ile alakalı yapılacak olan çalışmalar önemli bir ön veri niteliği taşımaktadır.

Keywords

vitamin d, hepatoselüler karsinom, 1.25(OH)2D3, HepG2

The Effect of Vitamin D on Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fourth most common cancer in terms of its incidence worldwide. The main causes of this type of cancer are Type II diabetes, obesity and alcohol. In this study, we aimed to determine the changes of both drug form and 1,25-dihydroxyvitamin [1,25(OH)2D3] form of vitamin D which is effective in liver diseases, but the interaction of cellular mechanisms is still unknown, on characteristics of HePG2 hepatocellular carcinoma cells. Both drug and 1,25(OH)2D3 form of vitamin D were applied separately to HepG2 cells and optimal concentrations and hours were determined. Then the proliferation, adhesion and immunohistochemically p53 amount of HepG2 cells were determined by the effects of both substances applied at the optimal concentration and hour. According to our obtained data, the optimal concentration and hour of each vitamin D substances was determined as 96th hour at 250 nM for drug form; 48th hour at 250 nM for 1,25(OH)2D3 form by observing the proliferation rates. It was determined that both drug and 1.25(OH)2D3 forms of vitamin D decreased adhesion of HepG2 cells statistically compared to the control group (p <0.001). When the changes in p53 amount of both vitamin D forms applied at optimal concentration and hour were examined immunohistochemically, it was observed that it decreased compared to control and sham groups. Our results provide preliminary data to ensure that vitamin D dose is maintained and controlled continuously when administered in hepatocellular cancer patients. Although it is an important vitamin to protect from some liver diseases; increasing proliferation in cancer cells, reducing adhesion and decreasing the amount of p53, a tumor suppressor, raises some questions about this subject. Furthermore, our results create a different perspective on the application of vitamin D on hepatocellular patients, and support important preliminary data for the studies to be conducted in the future.

Keywords

1.25(OH)2D3, Vitamin D, Hepatocellular Carcinoma, HePG2

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