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.
Highlights
Cervical cancer is the fourth most common cancer in women globally with 570,000 cases and 311,000 deaths estimated to occur in 2018, especially squamous cancer [1]
To explore whether mTOR participates in upregulation of Histone deacetylase 6 (HDAC6) expression induced by isoflurane, we found that p-mTOR protein expression was increased in both cells after the treatment with isoflurane (P < 0.05) (Fig. 3a, b)
The present study provides evidence that isoflurane promotes growth of cervical cancer cells, which are mediated by upregulation of HDAC6
Summary
Cervical cancer is the fourth most common cancer in women globally with 570,000 cases and 311,000 deaths estimated to occur in 2018, especially squamous cancer [1]. In spite of improvements in surgical techniques and radiation therapy for the management of cervical cancer, the prognosis remains poor. Emerging evidence has shown that perioperative factors including anesthesia technique and anesthetics may result in recurrence of cancer [2]. Limited data have demonstrated that the direct influence of anesthetics, especially inhalational ones on growth of tumor cells is contradictory [3,4,5]. Histone deacetylase 6 (HDAC6), originally known as a member of class IIb histone deacetylases family, implicated in multiple cellular processes related to cancer including carcinogenesis, tumor formation, cell adhesion, oncogenic transformation, motility, DNA damage response, cell survival, chaperone function, tumor aggressiveness, stress response, and anchorage-independent proliferation [6, 7].
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