2. Academic Validation
  3. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776

Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776

  • Exp Cell Res. 2017 Mar 15;352(2):403-411. doi: 10.1016/j.yexcr.2017.02.029.
Xiuxiu Hou 1,  Yunfang Yu 2,  Jianguo Feng 3,  Jiafeng Wang 4,  Chuanming Zheng 5,  Zhiqiang Ling 6,  Minghua Ge 7,  Xin Zhu 8
Affiliations

Affiliations

  • 1 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: show-1989@163.com.
  • 2 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: yyf_8247425@163.com.
  • 3 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: fengjg@zjcc.org.cn.
  • 4 Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: 15990081256@163.com.
  • 5 Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: mingdoc@163.com.
  • 6 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: lingzq@zjcc.org.cn.
  • 7 The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: gemh@zjcc.org.cn.
  • 8 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: zhuxin@zjcc.org.cn.
PMID: 28228352 DOI: 10.1016/j.yexcr.2017.02.029
Abstract

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.

Keywords

Apoptosis; Biomarker; Cell proliferation; Pim-1; SGI-1776; Salivary adenoid cystic carcinoma.

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