Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2017.58.349
The role and possible molecular mechanism of valproic acid in the growth of MCF-7 breast cancer cells
Xiao-jie Ma
; Department of Otorhinolaryngology, Qilu Hospitalof Shandong University, Jinan,Shandong, China
Yun-shan Wang
; Medical Research & Laboratory Diagnostic Center, Jinan CenterHospital Affiliated to ShandongUniversity, Jinan, Shandong, China
Wei-ping Gu
; Department of Pharmacy Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China
Xia Zhao
; Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China
Sažetak
Aim To investigate the role of valproic acid (VPA), a class I
selective histone deacetylase inhibitor, on Michigan Cancer
Foundation (MCF)-7 breast cancer cells, named and explore
its possible molecular mechanism.
Methods MCF-7 cells were cultured with sodium valproate
(0. 5-4.0 mmol/L) for 24 h, 48 h, and 72 h in vitro, respectively.
The cell viability, apoptosis, and cell cycle were examined.
The activities and protein expressions of caspase-3,
caspase-8, and caspase-9 were subsequently assayed. Finally,
mRNA and protein expressions of cyclin A, cyclin D1,
cyclin E, and p21 were analyzed.
Results Sodium valproate suppressed MCF-7 cell growth,
induced cell apoptosis, and arrested G1 phase in a timeand
concentration- dependent manner, with the relative
cell viabilities decreased, cell apoptosis ratios increased,
and percentage of G1 phase enhanced (P < 0.05). Increased
activity of caspase-3 and caspase-9, but not caspase-8, and
increased protein levels were found under sodium valproate
(2.0 mmol/L, 48h). P21 was up-regulated and cyclin
D1 was down-regulated at both mRNA and protein levels
under sodium valproate (2.0 mmol/L, 48h)(P < 0.05), although
cyclin E and cyclin A remained changed.
Conclusion These results indicate that VPA can suppress
the growth of breast cancer MCF-7 cells by inducing apoptosis
and arresting G1 phase. Intrinsic apoptotic pathway is
dominant for VPA-induced apoptosis. For G1 phase arrest,
p21 up-regulation and down-regulation of cyclin D1 may
be the main molecular mechanism.
Ključne riječi
Hrčak ID:
200211
URI
Datum izdavanja:
25.10.2017.
Posjeta: 903 *