Silencing of histone deacetylase 2 suppresses malignancy for proliferation, migration, and invasion of glioblastoma cells and enhances temozolomide sensitivity.
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells. Furthermore, silencing of HDAC2 can increase the sensitivity of GBM cells to temozolomide (TMZ), a standard-of-care during clinical GBM treatment. This might be due to that si-HDAC can significantly down-regulate the mRNA and protein expression of MRP1, while has no effect on ABCB1 and ABCG2. Schisandrin B (Sch B), a specific inhibitor of MRP1, can further increase the TMZ sensitivity in HDAC2-knocked down GBM cells. Collectively, our data revealed that targeted HDAC2 can suppress the malignancy of GBM cells and increase their sensitivity of TMZ via down-regulation of MRP1. It suggested that HDAC2 might be a potential target for GBM therapy and improvement in TMZ therapy efficiency.
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China. zhangzqgz@126.com.
Zhiqiang
Z
Zhang
Blood Center of Jining City, Jining, Shandong, 272000, China.
Yunmin
Y
Wang
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China.
Jiehan
J
Chen
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China.
Qijia
Q
Tan
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China.
Caijun
C
Xie
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China.
Cong
C
Li
Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medical), Dade Road No. 111, Yuexiu District, Guangzhou, 510120, China.
Wengang
W
Zhan
Guangdong 999 Brain Hospital, Guangzhou, 510510, China.
Mei
M
Wang
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology* / Q000628:therapy; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000502:physiology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D056464:Histone Deacetylase 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; D000077204:Temozolomide; C421109:multidrug resistance-associated protein 1
GBM; HDAC2; MRP1; Sensitivity; Temozolomide