Open AccessIsoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway
Author(s) -
Wenwen Zhang,
Fang Xue,
Shangdan Xie,
Cheng Chen,
Jingwei Li,
Xueqiong Zhu
Publication year - 2020
Publication title -
molecular and cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 124
eISSN - 1573-4919
pISSN - 0300-8177
DOI - 10.1007/s11010-020-03884-7
Subject(s) - histone deacetylase , histone deacetylase inhibitor , pi3k/akt/mtor pathway , cancer research , chemistry , protein kinase b , cell growth , hdac10 , microbiology and biotechnology , biology , histone , signal transduction , biochemistry , gene
This study investigated the effect of isoflurane on the proliferation of squamous cervical cancer cells, with focus on histone deacetylase 6 that is closely related to carcinogenesis. Squamous cervical cancer cells SiHa and Caski were exposed to 1%, 2%, or 3% isoflurane for 2 h, respectively. Cell proliferation was measured with the cell counting kit (CCK-8) assay and determined by BrdU assay. Expression of histone deacetylase 6, phospho-AKT, phospho-mTOR, and proliferating cell nuclear antigen (PCNA) was assessed by Western blot. In order to block the histone deacetylase 6 (HDAC6) expression, siRNA transfection was performed. Isoflurane significantly promoted the proliferation of both SiHa and Caski cells, accompanied by upregulation of PCNA protein expression. Isoflurane increased the level of histone deacetylase 6 protein expression in both cells, and knockdown of histone deacetylase 6 attenuated the pro-proliferation effects of isoflurane. Additionally, activation of AKT/mTOR was found after isoflurane treatment, and mTOR inhibition abolished isoflurane-induced histone deacetylase 6 expression. However, inhibition of AKT phosphorylation had no effect on the expression of histone deacetylase 6 mediated by isoflurane. In conclusion, Isoflurane enhanced proliferation of cervical cancer cells through upregulation of histone deacetylase 6, which was associated with mTOR-dependent pathway, but not AKT-mediated pathway.