title: Changes of Apolipoprotein M Gene Expression During the Cell Differentiation and Apoptosis Induced by Simvastatin in Combination with All-Trans Retinoic Acid in Human Promyelocytic Leukemia Cell Line NB4.
abstract: We examined the effect of simvastatin (SV) alone and in combination with all-trans retinoic acid (ATRA) on proliferation, differentiation, apoptosis and apolipoprotein M (apoM) expression in the human promyelocytic leukemia cell line NB4. The NB4 cells were incubated with 10 μM Simvastatin (10SV) and 0.5 μM ATRA alone or in combination, taking NB4 cells without any treatment as normal controls. The cells of different groups were collected at 24, 48 and 72 h post-incubation for further detection. Their morphological changes were observed after Wright stain. MTT method was used to assay the growth inhibition rate and flow cytometry to detect CD11b expression level and the early stage apoptosis ratio. Real-time quantitative reverse transcriptase-polymerase chain reaction was used to detect the apoM gene expression levels. As expected 0.5 μM ATRA did not affect proliferation or apoptosis, strongly induced differentiation and decreased apoM expression. 10SV inhibited proliferation, increased apoptosis, induced differentiation and increased apoM expression in a time-dependent manner. The addition of ATRA to SV did not increase the effect of SV on proliferation and apoptosis, but increased the effect of SV on differentiation. And completely abrogated the effect of SV on apoM expression. Together these results show that SV has anti-leukemic properties by itself and that combined therapy may have a place in the current anti-leukemic arsenal.
authors: Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Weiying
authors: W
authors: Gu
authors: Department of Hematology, The Center Hospital of Xuzhou, Xuzhou, 221009 China.
authors: Lili
authors: L
authors: Xiang
authors: Department of Hematology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, 545005 China.
authors: Tingxiu
authors: T
authors: Jiang
authors: Comprehensive Laboratory, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Guanghua
authors: G
authors: Luo
authors: Comprehensive Laboratory, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Jiang
authors: J
authors: Wei
authors: Jiangsu Institute of Hematology, The First Affiliated Hospital of Suzhou University, Suzhou, 215006 China.
authors: Jiannong
authors: J
authors: Cen
authors: Jiangsu Institute of Hematology, The First Affiliated Hospital of Suzhou University, Suzhou, 215006 China.
authors: Zixing
authors: Z
authors: Chen
authors: Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Guoqiang
authors: G
authors: Qiu
authors: Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Mei
authors: M
authors: Zeng
authors: Comprehensive Laboratory, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, 213003 China.
authors: Xiaoying
authors: X
authors: Zhang
keywords: All-trans retinoic acid; Apolipoprotein M gene; Cell apoptosis; NB4 cell; Simvastatin