异丙酚通过下调miR-24信号通路诱导乳腺癌细胞凋亡。

IF 1.9
Benxia Yu, Wei Gao, Hui Zhou, Xia Miao, Yuan Chang, Liping Wang, Miao Xu, Guangzhen Ni
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引用次数: 50

摘要

背景与目的:异丙酚,一种静脉麻醉药,已被发现能抑制乳腺癌细胞的生长。然而,其抗肿瘤机制尚不清楚。最近的一项研究发现,异丙酚可以显著下调miR-24在人类恶性肿瘤中的表达。在乳腺癌细胞中,miR-24过表达通过下调p27来促进细胞增殖,抑制细胞凋亡。据报道,miR-24在乳腺癌和乳腺癌细胞系中过表达。在本研究中,我们假设异丙酚通过miR-24/p27信号通路诱导乳腺癌细胞凋亡。方法:将乳腺癌MDA-MB-435细胞暴露于异丙酚(10 μM)中6小时,通过TUNEL染色、流式细胞术和cleaved caspase-3表达评估细胞死亡情况。采用定量逆转录聚合酶链反应(qRT-PCR)评估microRNA-24 (miR-24)表达。使用miR-24模拟物过表达miR-24。P27被一个小的干扰RNA敲除。Western blot检测p27和cleaved caspase-3的表达。结果:MDA-MB-435暴露于异丙酚后,凋亡细胞显著增加,miR-24下调,p27表达上调,cleaved caspase-3表达上调。靶向p27抑制异丙酚诱导的细胞凋亡miR-24过表达降低异丙酚诱导的细胞凋亡、裂解caspase-3和p27的表达。结论:异丙酚通过miR-24/p27信号通路失活诱导MDA-MB-435细胞死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Propofol induces apoptosis of breast cancer cells by downregulation of miR-24 signal pathway.

Background and objective: Propofol, an intravenous anesthetic agent, has been found to inhibit growth of breast cancer cells. However, the mechanisms underlying the antitumor are not known. A recent report has found that propofol could significantly downregulate miR-24 expression in the human malignant cancers. In breast cancer cells, overexpression of miR-24 promotes cell proliferation and inhibits cell apoptosis by downregulation of p27. The miR-24 has been reported to be overexpressed in breast cancer and breast cancer cell lines. In the present study, we hypothesized that propofol induces apoptosis of breast cancer cells by miR-24/p27 signal pathway.

Methods: Breast cancer MDA-MB-435 cells were exposed to propofol (10 μM) for 6 hr and cell death was assessed using TUNEL staining, Flow cytometry and cleaved caspase-3 expression. microRNA-24 (miR-24) expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-24 was overexpressed using a miR-24 mimic. P27 was knocked down using a small interfering RNA. p27 and cleaved caspase-3 expression was assessed by Western blot.

Results: MDA-MB-435 exposed to propofol showed a significant increase in apoptotic cells, followed by the downregulation of miR-24, upregulation of p27 expression and cleaved caspase-3 expression. Targeting p27 inhibits propofol-induced cell apoptosis; miR-24 overexpression decreased propofol-induced cell apoptosis, cleaved caspase-3 and p27 expression.

Conclusions: Propofol inducescell death in MDA-MB-435 cells via inactivation of miR-24/p27 signal pathway.

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