Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1

被引：49

作者：

Chen, Jian-Hui ^{[1
,2
]}

Zheng, Yu-Long ^{[2
]}

Xu, Chuan-Qin ^{[2
]}

Gu, Li-Zhi ^{[3
]}

Ding, Zong-Li ^{[2
]}

Qin, Ling ^{[1
]}

Wang, Yi ^{[2
]}

Fu, Ran ^{[2
]}

Wan, Yu-Feng ^{[2
]}

Hu, Cheng-Ping ^{[1
]}

机构：

[1] Cent S Univ, Dept Resp Med, Xiangya Hosp, Key Site Natl Clin Res Ctr Resp Dis, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[2] Huaian Second Peoples Hosp, Dept Resp Med, Huaian 223002, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Emergency Med, Huaian 223300, Jiangsu, Peoples R China

来源：

BIOLOGICAL CHEMISTRY | 2017年 / 398卷 / 07期

关键词：

ABCA1; DDP; HDAC2; NSCLC; VPA; HISTONE DEACETYLASE INHIBITOR; GENE-EXPRESSION; TRICHOSTATIN-A; IN-VIVO; RESISTANCE; LINES; DRUG; CHEMOSENSITIVITY; TRANSCRIPTION; INVOLVEMENT;

D O I：

10.1515/hsz-2016-0307

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

引用

页码：785 / 792

页数：8

共 37 条

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