Department of Anaesthesia, Mater Misericordiae University Hospital, School of Medicine & Medical Science University College Dublin, Ireland
Anticancer Res. 2014 Mar;34(3):1321-31.
It has been hypothesized that anaesthesia during primary breast cancer surgery may influence recurrence or metastasis. Effects of anaesthetic drugs on breast cancer cell function are unclear. The Neuroepithelial Cell Transforming Gene 1 (NET1) gene is associated with promoting migration in adenocarcinoma in vitro. Therefore, we investigated the role of NET1 in the effect of anaesthetic drugs propofol and bupivacaine on breast cancer cell function in vitro.
Estrogen receptor-negative (ER-negative) MDA-MB-231 and ER-positive MCF7 breast cancer cells were incubated with propofol (1-10 μg/ml) and bupivacaine (0.5-100 μg/ml) or control medium. Cell functions were determined with the CellTiter 96 Aqueous One Solution Cell Proliferation Assay, Chemotaxis 96-well Cell Migration and Invasion Assay. NET1 gene expression was determined by real-time PCR with gene silencing using siRNA and stimulation by lysophosphatidic acid (LPA).
Propofol did not reduce breast cancer cell proliferation of MCF7 or MDA-MB-231 cells. However, it did reduce migration of both MCF7 and MDA-MB-231 cells which was reversed by silencing NET1. Propofol reduced invasion of MCF7 but not of MDA-MB-231 cells, which was unaffected by siRNA. Propofol reduced expression of NET1 by 42-88% in MCF7 and by 49-79% in MDA-MB-231 cells. Bupivacaine had no significant effect on breast cancer cell function or NET1 expression.
Propofol reduced NET1 expression and cell migration in both ER-positive and -negative cells, which was reversed by silencing NET1, implying a role for NET1 in mediating the effect of propofol on breast cancer cell function in vitro.
有人假设原发性乳腺癌手术期间的麻醉可能会影响复发或转移。麻醉药物对乳腺癌细胞功能的影响尚不清楚。神经上皮细胞转化基因 1（NET1）基因与体外腺癌的促进迁移有关。因此，我们研究了 NET1 在麻醉药物异丙酚和布比卡因对体外乳腺癌细胞功能的影响中的作用。
雌激素受体阴性（ER-阴性）MDA-MB-231 和 ER 阳性 MCF7 乳腺癌细胞用异丙酚（1-10 μg/ml）和布比卡因（0.5-100 μg/ml）或对照培养基孵育。用 CellTiter 96 水性单溶液细胞增殖测定法、趋化性 96 孔细胞迁移和侵袭测定法测定细胞功能。通过实时 PCR 用 siRNA 基因沉默和溶血磷脂酸（LPA）刺激测定 NET1 基因表达。
异丙酚不会降低 MCF7 或 MDA-MB-231 细胞的乳腺癌细胞增殖。然而，它确实减少了 MCF7 和 MDA-MB-231 细胞的迁移，而 NET1 的沉默则逆转了这一现象。异丙酚减少了 MCF7 的侵袭，但对 MDA-MB-231 细胞没有影响，siRNA 对此没有影响。异丙酚使 MCF7 中 NET1 的表达降低了 42-88%，MDA-MB-231 细胞中降低了 49-79%。布比卡因对乳腺癌细胞功能或 NET1 表达没有显著影响。
异丙酚降低了 ER 阳性和阴性细胞中 NET1 的表达和细胞迁移，NET1 的沉默逆转了这一现象，表明 NET1 在介导异丙酚对体外乳腺癌细胞功能的影响中起作用。
