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

Cited By: 2

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

Supporting Institution

MALTEPE ÜNİVERSİTESİ BİLİMSEL ARAŞTIRMA PROJE KOMİSYONU

Thanks

Bu çalışma Maltepe Üniversitesi Bilimsel Araştırma Proje komisyonu tarafından desteklenmektedir.

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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