Hou Xiuxiu, Yu Yunfang, Feng Jianguo, Wang Jiafeng, Zheng Chuanming, Ling Zhiqiang, Ge Minghua, Zhu Xin
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China.
Exp Cell Res. 2017 Mar 15;352(2):403-411. doi: 10.1016/j.yexcr.2017.02.029. Epub 2017 Feb 20.
Provirus integration site for Moloney murine leukemia virus 1 (Pim-1) has proved to be an oncogene and it is known that to depress Pim-1 activity may be a novel oncological treatment strategy. SGI-1776, a small molecule, is the first clinically tested inhibitor of the Pim kinase family. Here, we aimed to explore the effect of SGI-1776 on salivary adenoid cystic carcinoma (SACC). Expression of Pim-1 was confirmed in SACC and control tissues by qRT-PCR. After SGI-1776 treatment, the Pim-1 expressions and Pim-1 kinase activity in both SACC-83 and SACC-LM cell lines were measured. Cell proliferation, cell invasion, cell cycle, apoptosis and mitochondrial membrane potential were analyzed. Also, the expression of FOXO3a, p-FOXO3a, RUNX3, Bcl-2, BAD, p-BAD, Bim and p-Bim were detected by Western blot. The results showed that Pim-1 was significantly overexpressed in SACC tissues. SGI-1776 down-regulated the Pim-1 expression, inhibited Pim-1 kinase activity, reduced cell proliferation, decreased invasive ability, increased caspase-3 activity and induced apoptosis, cell cycle arrest and mitochondrial depolarization. Reduced expression was also seen in p-FOXO3a, RUNX3, Bcl-2, p-BAD and p-Bim, whereas no significant changes were observed from FOXO3a, BAD and Bim. These results confirm the pivotal role of Pim-1 in SACC and suggest that targeting Pim-1 kinase signal pathway by SGI-1776 might be a promising therapeutic modality for SACC.
莫洛尼鼠白血病病毒1原病毒整合位点（Pim-1）已被证明是一种致癌基因，并且已知抑制Pim-1活性可能是一种新型的肿瘤治疗策略。小分子SGI-1776是首个进入临床试验的Pim激酶家族抑制剂。在此，我们旨在探究SGI-1776对涎腺腺样囊性癌（SACC）的影响。通过qRT-PCR在SACC和对照组织中证实了Pim-1的表达。在SGI-1776处理后，检测了SACC-83和SACC-LM细胞系中的Pim-1表达及Pim-1激酶活性。分析了细胞增殖、细胞侵袭、细胞周期、凋亡和线粒体膜电位。此外，通过蛋白质免疫印迹法检测了FOXO3a、p-FOXO3a、RUNX3、Bcl-2、BAD、p-BAD、Bim和p-Bim的表达。结果显示，Pim-1在SACC组织中显著过表达。SGI-1776下调了Pim-1表达，抑制了Pim-1激酶活性，降低了细胞增殖，减弱了侵袭能力，增加了caspase-3活性并诱导了凋亡、细胞周期阻滞和线粒体去极化。p-FOXO3a、RUNX3、Bcl-2、p-BAD和p-Bim的表达也降低，而FOXO3a、BAD和Bim未观察到显著变化。这些结果证实了Pim-1在SACC中的关键作用，并表明通过SGI-1776靶向Pim-1激酶信号通路可能是SACC一种有前景的治疗方式。
