中国临床药理学杂志2024，Vol.40Issue(11)：1578-1582,5.DOI:10.13699/j.cnki.1001-6821.2024.11.008
1-磷酸鞘氨醇信号激活对乳腺癌BT549细胞增殖的影响
Role of sphingosine-1-phosphate signaling in the proliferation of breast cancer BT549 cells
摘要
Abstract
Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.关键词
1-磷酸鞘氨醇受体激动药和拮抗药/蛋白激酶B信号通路抑制药/1-磷酸鞘氨醇信号/乳腺癌细胞/增殖Key words
sphingosine 1-phosphate receptor agonist and antagonist/protein kinase B inhibitor/sphingosine 1-phosphate signaling/breast cancer cell/proliferation分类
医药卫生引用本文复制引用
宋娟,王明,刘欣洋,张浩天,张奇,赵学梅,刘颖,崔红霞..1-磷酸鞘氨醇信号激活对乳腺癌BT549细胞增殖的影响[J].中国临床药理学杂志,2024,40(11):1578-1582,5.基金项目
黑龙江省省属高等学校基本科研业务费科研基金资助项目(2019-KYYWF-1240) （2019-KYYWF-1240）
齐齐哈尔市科技计划联合引导基金资助项目(LHYD-202019) （LHYD-202019）
