Albrechtsson Elin, Jonsson Tord, Möller Sebastian, Höglund Mattias, Ohlsson Bodil, Axelson Jan
Department of Surgery, Lund University, Sweden.
Pancreatology. 2003;3(1):41-6. doi: 10.1159/000069149.
The vitamin D-receptor (VDR) has been detected in both normal and malignant cells of different tissues. Treatment with vitamin D(3) has been suggested as a possible therapy in malignant diseases such as pancreatic cancer. Synthetic analogues of vitamin D(3) have a less hypercalcemic effect than native vitamin D(3). The aim was to study the expression of the VDR in human pancreatic cancers and to study the in vitro effect of an analogue to vitamin D(3) on cell lines established from these cancers.
The pancreatic cancer cell lines were established from primary cultures with only cancer cells. A probe specific for the human VDR was used. After reverse-transcriptase PCR and Northern blotting, the expression of the VDR in normal pancreas and in pancreatic cancers was compared. The cell lines were incubated with EB 1089, a synthetic analogue vitamin of D(3), in dose-response studies. The cell number was measured by the XTT colorimetric method.
The VDR was expressed in all cancers and in six of the cell lines the expression was increased more than 3-fold compared to normal pancreas. All cell lines developed from human pancreatic cancers responded with a decreased cell number to the vitamin D(3) analogue at concentrations of 10(-5) M or higher.
The VDR was expressed in all pancreatic cancers studied. Cell lines derived from these cancers responded with a decrease in cell number to high concentrations of a vitamin D(3) analogue. These results, and the doses to use, have to be confirmed with in vivo studies.
在不同组织的正常细胞和恶性细胞中均检测到维生素D受体(VDR)。维生素D₃治疗已被提议作为胰腺癌等恶性疾病的一种可能疗法。维生素D₃的合成类似物比天然维生素D₃具有更低的高钙血症效应。本研究旨在探讨VDR在人胰腺癌中的表达情况,并研究一种维生素D₃类似物对源自这些癌症的细胞系的体外作用。
从仅含癌细胞的原代培养物中建立胰腺癌细胞系。使用针对人VDR的特异性探针。经过逆转录聚合酶链反应(RT-PCR)和Northern印迹分析,比较VDR在正常胰腺和胰腺癌中的表达。在剂量反应研究中,将细胞系与维生素D₃的合成类似物EB 1089孵育。通过XTT比色法测量细胞数量。
所有癌症中均检测到VDR表达,在六个细胞系中,与正常胰腺相比,VDR表达增加了3倍以上。源自人胰腺癌的所有细胞系在10⁻⁵M或更高浓度的维生素D₃类似物作用下,细胞数量均减少。
在所研究的所有胰腺癌中均检测到VDR表达。源自这些癌症的细胞系在高浓度维生素D₃类似物作用下细胞数量减少。这些结果以及所用剂量必须通过体内研究加以证实。