Effects and mechanisms of histone deacetylase inhibitors on invasion and metastasis of Her2 positive breast cancer cell / 中国医师杂志

ABSTRACT

Objective To investigate the effect of histone deacetylase inhibitor on Her2 positive breast cancer cell line BT474 and SKBR3 in apoptosis and metastasis.Methods Histone deacetylase inhibitor MS-275,suberoylanilide hydroxamic acid (SAHA)(4 μmol/L,and 50 μmol/iL,respectively) treated the cell lines BT474 and SKBR3 cells.Flow cytometer examined the apoptosis ratio.Transwell tested their metastatic activity.Western blot assay was performed to detect the associated proteins.Results SAHA and MS-275 inhibited the cell survival.The BT474 cell survival was (39 ± 11) ％,(54 ± 8) ％,and the SKBR3 survival was (62 ± 6) ％,(71 ± 9) ％,according to the fluorescence-activated cell sorting (FACS) result.SAHA and MS-275 induced the BT474 cell apoptosis 8.46± 0.28 (P ＜0.01),4.15 ± 0.71 (P ＜0.01) fold change,respectively;and upregulated the SKBR3 cell apoptosis ratio 5.51 ± 1.24 (P ＜0.01),4.04 ±0.69 (P ＜0.01) fold.The Transwell result showed that SAHA,MS-275 inhibited the Transwell ability of BT474 from the control 184.7 ± 18.8 to 104.3 ± 7.1,131.3 ±9.1 per view,and the SKBR3 from control 60 ± 16.7 per view to 14.3 ± 6.5,34.3 ± 8.7 per view.The Western blot result showed that SAHA,MS-275 inhibited the protein level of vimentin,Her2,β-catenin,histone deacetylase inhibitor (HDACi),and upregulated the acetylation level of histone 3.The E-caherin protein was regulated in BT474 and SKBR3 cells.Conclusions MS-275,SAHA can induce BT474 and SKBR3 apoptosis significantly,also inhibit their metastatic activity.