[维生素D在人肝细胞癌及周围非肿瘤性肝脏中的代谢与信号传导]
[Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver].
作者信息
Horváth Evelin, Balla Bernadett, Kósa János, Lakatos Péter András, Lazáry Áron, Németh Dániel, Jozilan Hasan, Somorácz Áron, Korompay Anna, Gyöngyösi Benedek, Borka Katalin, Kiss András, Kupcsulik Péter, Schaff Zsuzsa, Szalay Ferenc
机构信息
I. Belgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Korányi Sándor u. 2/A, 1083.
Országos Gerincgyógyászati Központ Budapest.
出版信息
Orv Hetil. 2016 Nov;157(48):1910-1918. doi: 10.1556/650.2016.30592.
INTRODUCTION
1,25-Dihydroxy vitamin D mediates antitumor effects in hepatocellular carcinoma.
AIM
We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver.
METHODS
Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry.
RESULTS
Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis.
CONCLUSIONS
The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.
引言
1,25 - 二羟基维生素D介导肝细胞癌的抗肿瘤作用。
目的
我们研究了人肝细胞癌与周围非肿瘤性肝组织中1,25 - 二羟基维生素D失活酶CYP24A1、激活酶CYP27B1的mRNA以及维生素D受体（VDR）的mRNA和蛋白表达差异。
方法
对13例患者的速冻组织进行CYP24A1的mRNA和蛋白表达研究。对36例患者的石蜡包埋组织用于研究VDR和CYP27B1的mRNA。通过逆转录 - 聚合酶链反应（RT - PCR）测量mRNA表达，通过免疫组织化学检测CYP24A1蛋白。
结果
与非肿瘤性肝组织相比，肝细胞癌中VDR和CYP27B1的表达显著降低（p<0.05）。大多数肝癌样本表达CYP24A1 mRNA，但非肿瘤性肝组织均未表达。基因激活后伴随着CYP24A1蛋白合成。
结论
人肝细胞癌样本中CYP24A1 mRNA的存在以及VDR和CYP27B1 mRNA表达的降低表明1,25 - 二羟基维生素D的生物利用度降低，提供了一种逃避抗肿瘤作用的机制。《匈牙利医学周报》，2016年，157(48)，1910 - 1918。
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