Sun Zhenni, Yue Lu, Shen Zan, Li Yong, Sui Aihua, Li Tianjun, Tang Qian, Yao Ruyong, Sun Yongning
Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266003, P.R. China.
Department of Oncology, The Sixth People's Hospital, Medical College of Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
Oncol Lett. 2017 Apr;13(4):2377-2384. doi: 10.3892/ol.2017.5722. Epub 2017 Feb 13.
Nucleophosmin (NPM) and human epidermal growth factor receptor-2 (Her-2) are abnormally expressed in various types of human malignant tumors, including gastric cancer, and have been closely associated with cancer chemoresistance. However, their interaction and roles in oxaliplatin resistance are not fully understood. Therefore, the present study aimed to elucidate the relationship between NPM and Her-2 in gastric cancer cell lines and clinical samples, and further investigated their role in the resistance of gastric cancer to oxaliplatin. Western blotting and reverse transcription-quantitative polymerase chain reaction confirmed that NPM and Her-2 expression were significantly upregulated in gastric cancer cells and clinical samples, and that their expression levels were strongly correlated. However, Her-2 expression was not affected by upregulation or downregulation of NPM expression in gastric cancer cells. Cell counting kit-8 assays demonstrated that the cell sensitivity to oxaliplatin decreased simultaneously with an increase in NPM expression. Furthermore, inhibition of Her-2 expression using trastuzumab significantly increased the sensitivity of the cells to oxaliplatin, which occurred simultaneously with the downregulation of NPM. These results indicated that inhibition of NPM, as a Her-2 downstream signal, may be a novel strategy to overcome oxaliplatin-resistant gastric cancer, and that trastuzumab and oxaliplatin may exhibit a synergistic antitumor effect in Her-2-positive gastric cancer cells.
核磷蛋白（NPM）和人表皮生长因子受体2（Her-2）在包括胃癌在内的多种人类恶性肿瘤中异常表达，并且与癌症化疗耐药性密切相关。然而，它们在奥沙利铂耐药中的相互作用和作用尚未完全明确。因此，本研究旨在阐明胃癌细胞系和临床样本中NPM与Her-2之间的关系，并进一步研究它们在胃癌对奥沙利铂耐药中的作用。蛋白质免疫印迹法和逆转录定量聚合酶链反应证实，NPM和Her-2在胃癌细胞和临床样本中的表达显著上调，且它们的表达水平呈强相关。然而，胃癌细胞中NPM表达的上调或下调并不影响Her-2的表达。细胞计数试剂盒-8检测表明，细胞对奥沙利铂的敏感性随着NPM表达的增加而同时降低。此外，使用曲妥珠单抗抑制Her-2表达显著增加了细胞对奥沙利铂的敏感性，这与NPM的下调同时发生。这些结果表明，抑制作为Her-2下游信号的NPM可能是克服奥沙利铂耐药性胃癌的一种新策略，并且曲妥珠单抗和奥沙利铂可能在Her-2阳性胃癌细胞中表现出协同抗肿瘤作用。
