The effects of histone methyltransferase inhibitor UNC1999 on proliferation and migration of breast cancer cells
ZENG Junjie
ZHENG Xiaodong
Abstract：Objective To investigate the effects and mechanism of proliferation and migration of MDA-MB-231 cells by histone methyltransferase inhibitor UNC1999. Methods UNC1999, UNC2400 and Vehicle groups were treated with UNC1999, control compound of UNC1999 and DMSO, respectively. After 48 h treatment, immunoblotting was performed to manifest inhibitory effect of UNC1999 on histone lysine 27 tri-methylation (H3 K27 me3) as well as expression of PI3 kinasecatalytic subunit p110α and p-ERK involved in PI3 K/ERK pathway. MTS and cell number counting assays were performed to detect the proliferation capacity. Transwell was performed to detect the cell migration, and the apoptosis and cell cycle was detected by cell flow cytometry. Results After 48 h treatment, H3 K27 me3 in MDA-MB-231 cells treated with 5 μmol/L UNC1999 was significantly decreased by 63％ compared with UNC2400 and Vehicle groups (P ＜ 0. 05). Additionally, no pronounced difference was detected between UNC2400 and Vehicle groups (P＞ 0. 05). The proliferation of UNC1999-treated group was inhibited remarkably compared with UNC2400 group (P ＜ 0. 05). The number of cells passing through the Transwell chamber was 91. 0 ± 2. 28 when treated with UNC1999, which was significantly different from that of 211. 6 ± 8. 69 in Vehicle group and 207. 2 ± 10. 19 in UNC2400 group (P ＜ 0. 05). However, no difference was detected between UNC2400 and Vehicle groups (P＞ 0. 05). After treatment with UNC1999 for 48 h, a large number of cells stagnated in G0/G1 phase, while cells in S phase decreased significantly, and cell apoptosis increased. Mechanistically, UNC1999 decreased p110αand p-ERK by 59％ and 50％, respectively (P ＜ 0. 05). Conclusion UNC1999 inhibits proliferation and migration of breast cancer cells while promotes apoptosis, at least partially, through decreasing p110α and p-ERK level involved in PI3 K/ERK pathway.
Keywords：Breast cancerHistone methyltransferaseProliferationMigrationApoptosisPI3K/ERK signal pathway
Publication Date：2019-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1-6 )