title: Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776.
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.
authors.affiliation: 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.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Hou
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: yyf_8247425@163.com.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: fengjg@zjcc.org.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: 15990081256@163.com.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: mingdoc@163.com.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: lingzq@zjcc.org.cn.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ling
authors.affiliation: 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.
authors.forename: Minghua
authors.initials: M
authors.lastname: Ge
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Hangzhou 310022, China. Electronic address: zhuxin@zjcc.org.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000494:pharmacology*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C545188:SGI 1776; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1
keywords: Apoptosis; Biomarker; Cell proliferation; Pim-1; SGI-1776; Salivary adenoid cystic carcinoma