title: [Effects of simvastatin on PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1].
abstract: To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (SV) on proliferation, apoptosis and the PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1. SHI-1 cells were incubated with different concentrations of SV (5, 10, 15 µmol/L). Otherwise, SHI-1 cells without any treatment were used as control. Cells in different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to assay the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis ratio. The human PI3K-AKT Signaling Pathway RT(2) Profiler(TM) PCR Array was used to detect the expression of 84 genes involved in PI3K-AKT signaling. The results indicated that the SV inhibited the proliferation and inducted the apoptosis of SHI-1 cells in time- and dose-dependent manners significantly. The growth inhibition rates of SHI-1 cells treated with 15 µmol/L SV for 24, 48 and 72 h were 26.82, 47.09 and 63.92, respectively; and their early stage apoptosis ratios were 5.75, 13.25 and 15.59, respectively. Compared with the control group, expression levels of 39 genes were changed in the group of 15 µmol/L SV at 48 h, among them 26 genes were down-regulated and 13 genes were up-regulated. It is concluded that the SV can inhibit proliferation and induce apoptosis of SHI-1 cells, and the mechanism may be associated with the changes of gene expression level in PI3K-AKT signaling pathway regulated by SV.
authors.affiliation: Department of Hematology, Third Affiliated Hospital of Suzhou University, Changzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Gu
authors.forename: Ting-Xiu
authors.initials: TX
authors.lastname: Jiang
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Chen
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Qiu
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Hao-Qing
authors.initials: HQ
authors.lastname: Wu
authors.forename: Zhi-Lin
authors.initials: ZL
authors.lastname: Wang
authors.forename: Xiao-Bao
authors.initials: XB
authors.lastname: Xie
authors.forename: Xiang-Shan
authors.initials: XS
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019821:Simvastatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt