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.

中文翻译：

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异氟醚通过 mTOR-组蛋白脱乙酰酶 6 通路促进宫颈鳞癌细胞增殖。

本研究探讨异氟醚对宫颈鳞癌细胞增殖的影响，重点研究与致癌作用密切相关的组蛋白去乙酰化酶6。鳞状宫颈癌细胞 SiHa 和 Caski 分别暴露于 1%、2% 或 3% 的异氟醚 2 小时。使用细胞计数试剂盒（CCK-8）测定法测量细胞增殖并通过BrdU测定法测定。通过蛋白质印迹评估组蛋白去乙酰化酶 6、磷酸化 AKT、磷酸化 mTOR 和增殖细胞核抗原 (PCNA) 的表达。为了阻断组蛋白去乙酰化酶 6 (HDAC6) 的表达，进行了 siRNA 转染。异氟醚显着促进 SiHa 和 Caski 细胞的增殖，伴随着 PCNA 蛋白表达的上调。异氟醚增加了两种细胞中组蛋白脱乙酰酶 6 蛋白的表达水平，组蛋白脱乙酰酶 6 的敲低减弱了异氟醚的促增殖作用。此外，在异氟醚处理后发现 AKT/mTOR 的激活，并且 mTOR 抑制消除了异氟醚诱导的组蛋白脱乙酰酶 6 表达。然而，抑制 AKT 磷酸化对异氟醚介导的组蛋白脱乙酰酶 6 的表达没有影响。总之，异氟醚通过上调组蛋白去乙酰化酶 6 增强宫颈癌细胞的增殖，这与 mTOR 依赖性途径有关，但与 AKT 介导的途径无关。和 mTOR 抑制消除了异氟醚诱导的组蛋白脱乙酰酶 6 表达。然而，抑制 AKT 磷酸化对异氟醚介导的组蛋白脱乙酰酶 6 的表达没有影响。总之，异氟醚通过上调组蛋白去乙酰化酶 6 增强宫颈癌细胞的增殖，这与 mTOR 依赖性途径有关，但与 AKT 介导的途径无关。和 mTOR 抑制消除了异氟醚诱导的组蛋白脱乙酰酶 6 表达。然而，抑制 AKT 磷酸化对异氟醚介导的组蛋白脱乙酰酶 6 的表达没有影响。总之，异氟醚通过上调组蛋白去乙酰化酶 6 增强宫颈癌细胞的增殖，这与 mTOR 依赖性途径有关，但与 AKT 介导的途径无关。