Shan Bin, Dong Mei, Tang He, Wang Na, Zhang Jin, Yan Changqing, Jiao Xiaocui, Zhang Hailin, Wang Chuan
Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Department of Surgery, The Affiliated Hospital of Hebei Science and Technology University, Shijiazhuang, Hebei 050018, P.R. China.
Oncol Lett. 2014 Jul;8(1):345-350. doi: 10.3892/ol.2014.2110. Epub 2014 May 2.
Voltage-gated sodium channels (VGSCs) are expressed not only in excitable cells but also in numerous metastatic cells, particularly in certain types of cancer cells. In some types of cancer, including prostate cancer, the expression of VGSCs is associated with cancer migration, invasion and metastasis . However, the detailed expression profiles of VGSC α subunits in normal human prostate, in prostatic hyperplasia and prostatic cancer remain controversial. In the present study, quantitative polymerase chain reaction was used to systematically detect all subtypes of VGSC α subunits in normal human prostate, benign prostatic hyperplasia (BPH) and prostate cancer cells. The expression profile of VGSC α subunits was observed to differ between these cell types. Nav1.5 was the major isoform expressed in normal human prostate tissue, while Nav1.5 and Nav1.2 were the predominant isoforms in BPH tissue. However, in PC-3 and LNCaP cells, two typical prostate cancer cell lines, Nav1.6 and Nav1.7 were abundantly expressed. By comparing the relative expression levels of Nav1.5, Nav1.6 and Nav1.7 in these cells, the mRNA levels of Nav1.6 and Nav1.7 were identified to be 6- to 27-fold higher in PC-3 and LNCaP cells than in either normal or BPH samples (P<0.05); however, Nav1.5 mRNA levels were relatively lower compared with those of Nav1.6 or Nav1.7 in all cells analyzed. To confirm whether Nav1.6 and Nav1.7 expression in cancer cells was functional, a patch-clamp technique was used to record whole-cell currents. A tetrodotoxin-sensitive sodium current was successfully recorded in PC-3 cells, but not in LNCaP cells. It was concluded that although all types of VGSC α subunits exhibited low expression levels in normal prostate and BPH cells, both Nav1.6 and Nav1.7 were significantly upregulated in the prostate cancer cell lines, suggesting these subtypes may be potential diagnostic markers and therapeutic targets for certain types of prostate cancer in humans.
电压门控钠通道（VGSCs）不仅在可兴奋细胞中表达，还在许多转移细胞中表达，尤其是在某些类型的癌细胞中。在包括前列腺癌在内的某些癌症类型中，VGSCs的表达与癌症迁移、侵袭和转移有关。然而，正常人前列腺、前列腺增生和前列腺癌中VGSCα亚基的详细表达谱仍存在争议。在本研究中，采用定量聚合酶链反应系统检测正常人前列腺、良性前列腺增生（BPH）和前列腺癌细胞中VGSCα亚基的所有亚型。观察到这些细胞类型之间VGSCα亚基的表达谱不同。Nav1.5是正常人前列腺组织中表达的主要亚型，而Nav1.5和Nav1.2是BPH组织中的主要亚型。然而，在两种典型的前列腺癌细胞系PC-3和LNCaP细胞中，Nav1.6和Nav1.7大量表达。通过比较这些细胞中Nav1.5、Nav1.6和Nav1.7的相对表达水平，发现PC-3和LNCaP细胞中Nav1.6和Nav1.7的mRNA水平比正常或BPH样本高6至27倍（P<0.05）；然而，在所有分析的细胞中，Nav1.5的mRNA水平与Nav1.6或Nav1.7相比相对较低。为了确认癌细胞中Nav1.6和Nav1.7的表达是否具有功能，采用膜片钳技术记录全细胞电流。在PC-3细胞中成功记录到河豚毒素敏感的钠电流，但在LNCaP细胞中未记录到。得出的结论是，尽管所有类型的VGSCα亚基在正常前列腺和BPH细胞中表达水平较低，但Nav1.6和Nav1.7在前列腺癌细胞系中均显著上调，表明这些亚型可能是人类某些类型前列腺癌的潜在诊断标志物和治疗靶点。
