Acute Abdominal Surgery Ward, Affiliated ZhongShan Hospital Dalian University, Dalian City, Liaoning Province, China.
General Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an City, Jiangsu Province, China.
J Pharm Pharmacol. 2021 Apr 27;73(6):740-748. doi: 10.1093/jpp/rgab010.
To assess nuclear protein 1 (NUPR1) level in human gastric cancer (GC) cells, explore the effects of NUPR1 on GC progression, and investigate the possible regulatory mechanism.
Immunohistochemistry (IHC), Immunoblot and quantitative PCR assays were conducted to detect the NUPR1 level in human GC tissues and corresponding normal tissues. Also, NUPR1 expression level correlates with clinical features of GC patients. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), transwell assays, Immunoblot assays, and flow cytometry (FCM) assays were used to evaluate the effects of NUPR1 on the proliferation, invasion, epithelial-mesenchymal transformation (EMT) and apoptosis of GC cells in vitro. Immunoblot assays were performed to detect the potential mechanism in NUPR1-mediated drug resistance.
We found the expression of NUPR1 was upregulated in human gastric cancer tissues and correlated with the clinical features including tumour size, tumour stage and, lymph node metastasis. We further noticed that the depletion of NUPR1 inhibited the invasion and EMT of gastric cancer cells and stimulated the apoptosis. In doxorubicin-resistant gastric cancer cells, yes-associated protein (YAP) activation was up-regulated, and YAP could regulate the expression of NUPR1 to affect drug-resistance. We further provided the evidence that overexpression of NUPR1 reversed the effect of YAP knockdown on cell malignancy and drug resistance via regulating AKT and p21 pathway.
Our findings indicated the involvement of NUPR1 in the progression of gastric cancer and elucidated its molecular mechanism in regulating drug resistance.
检测核蛋白 1（NUPR1）在人胃癌（GC）细胞中的水平，探讨 NUPR1 对 GC 进展的影响，并研究可能的调控机制。
采用免疫组织化学（IHC）、免疫印迹和实时定量 PCR 检测人 GC 组织及相应正常组织中 NUPR1 的水平，分析 NUPR1 表达水平与 GC 患者临床特征的相关性。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法、Transwell 实验、免疫印迹和流式细胞术（FCM）检测 NUPR1 对 GC 细胞体外增殖、侵袭、上皮间质转化（EMT）和凋亡的影响。免疫印迹检测 NUPR1 介导的耐药潜在机制。
我们发现 NUPR1 在人胃癌组织中表达上调，并与肿瘤大小、肿瘤分期和淋巴结转移等临床特征相关。进一步研究发现，敲低 NUPR1 抑制了胃癌细胞的侵袭和 EMT，并促进了凋亡。在多柔比星耐药的胃癌细胞中，Yes 相关蛋白（YAP）激活上调，YAP 可调节 NUPR1 的表达，影响耐药性。我们进一步提供了证据表明，过表达 NUPR1 可通过调节 AKT 和 p21 通路，逆转 YAP 敲低对细胞恶性程度和耐药性的影响。
我们的研究结果表明 NUPR1 参与了胃癌的进展，并阐明了其在调节耐药性方面的分子机制。
