1. Academic Validation
  2. Isoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway

Isoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway

  • Mol Cell Biochem. 2021 Jan;476(1):45-55. doi: 10.1007/s11010-020-03884-7.
Wenwen Zhang  # 1 Fang Xue  # 1 Shangdan Xie 1 Cheng Chen 1 Jingwei Li 1 Xueqiong Zhu 2
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China.
  • 2 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China. [email protected].
  • # Contributed equally.
Abstract

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.

Keywords

Cervical cancer; Histone deacetylase 6; Isoflurane; Proliferation; mTOR.

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