Heinzman Zachary, Schmidt Connor, Sliwinski Marek K, Goonesekere Nalin C W
Department of Chemistry and Biochemistry, University of Northern Iowa, Cedar Falls, IA 50614, USA.
Department of Biology, University of Northern Iowa, Cedar Falls, IA 50614, USA.
Pharmaceuticals (Basel). 2021 Mar 3;14(3):209. doi: 10.3390/ph14030209.
The high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of pancreatic cancer cell lines and in early-stage paired patient tissue samples (normal and diseased) by quantitative reverse transcription-PCR (qRT-PCR). We also investigated the effect of 1,2,3,4,6-penta--galloyl-β-d-glucopyranoside (PGG) as a therapeutic agent for PC. We find that GNMT is markedly downregulated ( < 0.05), in a majority of PC cell lines. Similar results are observed in early-stage patient tissue samples, where GNMT expression can be reduced by a 100-fold or more. We also show that PGG is a strong inhibitor of PC cell proliferation, with an IC value of 12 ng/mL, and PGG upregulates GNMT expression in a dose-dependent manner. In conclusion, our data show that GNMT has promise as a biomarker and as a therapeutic target for PC.
胰腺癌（PC）的高死亡率归因于肿瘤早期缺乏特异性症状以及其高生物学侵袭性。可靠的生物标志物和新的治疗靶点将有助于改善胰腺癌的预后。在本研究中，我们通过定量逆转录 - 聚合酶链反应（qRT-PCR）分析了甘氨酸N-甲基转移酶（GNMT）在一组胰腺癌细胞系以及早期配对患者组织样本（正常和病变）中的表达。我们还研究了1,2,3,4,6 - 五没食子酰基 - β - D - 吡喃葡萄糖苷（PGG）作为胰腺癌治疗药物的效果。我们发现，在大多数胰腺癌细胞系中，GNMT明显下调（<0.05）。在早期患者组织样本中也观察到类似结果，其中GNMT表达可降低100倍或更多。我们还表明，PGG是胰腺癌细胞增殖的强效抑制剂，IC值为12 ng/mL，并且PGG以剂量依赖性方式上调GNMT表达。总之，我们的数据表明GNMT有望作为胰腺癌的生物标志物和治疗靶点。
