不同麻醉药对人乳腺癌细胞侵袭与迁移能力的影响

发布时间：2018-10-31 16:05

【摘要】：目的：乳腺癌是女性最常见的恶性肿瘤之一，其发病率呈逐年上升趋势，且发病年龄逐渐年轻化，术后转移和复发是其最主要的死亡原因。人乳腺癌细胞株MDA-MB-231是人乳腺癌细胞的一种分型，属于三阴乳腺癌，即雌激素受体、孕激素受体以及人表皮生长因子受体均为阴性的乳腺癌。“三阴乳腺癌”生物学特征为导管癌，肿瘤侵袭性很强，，易发生局部侵袭、远处转移和复发，且发病年龄较小，Nottingham预后指数(NPI)差，其治疗方法首选手术治疗和化疗，对内分泌治疗以及靶向治疗效果较差。针对此类患者，在围术期如何抑制肿瘤的侵袭与转移已成为目前临床研究的重点。现阶段研究表明，麻醉对恶性肿瘤侵袭和迁移有一定的影响。作为临床常用的麻醉药物异丙酚和七氟烷，相关研究显示二者对恶性肿瘤侵袭和迁移的影响不同。但对于“三阴乳腺癌”，异丙酚和七氟烷对其侵袭和迁移的影响如何，尚无相关研究。本研究选取人乳腺癌细胞株MDA-MB-231，观察静脉麻醉药异丙酚和吸入麻醉药七氟烷对其侵袭和迁移能力的影响以及可能的机制。 方法：人乳腺癌细胞株MDA-MB-231接种于培养板，培养24h后，随机将其分为3组：对照组（C组）、异丙酚组（P组）、七氟烷组（S组）。所有实验用细胞均处于对数生长期。将培养板置于无菌密闭容器内，置于37℃恒温水浴锅中。密闭容器进气口连接麻醉机，出气口连接麻醉气体监测仪。对照组通入95%O2-5%CO2混合气体1L/min，孵育6h；异丙酚组加入5μg/ml异丙酚，同时通入95%O2-5%CO2混合气体1L/min，孵育6h；七氟烷组通入95%O2-5%CO2混合气体1L/min和3.4%V/V七氟烷，孵育6h；每组细胞处理完毕后，放回37℃、5%CO2培养箱中，培养24h，备用。采用Transwell侵袭实验法检测细胞的侵袭能力，采用细胞划痕实验法检测细胞的迁移运动能力，采用Western blot法检测基质金属蛋白酶-9(MMP-9)的表达。 结果：Transwell侵袭实验结果显示，与C组相比，5μg/ml异丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231细胞6h，穿过Transwell小室的细胞数均减少（P＜0.05）。P组和S组之间比较，穿过Transwell小室的细胞数无差别（P＞0.05）。 细胞划痕实验结果显示，与C组相比，5μg/ml异丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231细胞6h，均可使该细胞的迁移率降低（P＜0.05），P组与S组之间比较，细胞迁移率差异无统计学意义（P＞0.05）。 Western blot实验结果示，与C组相比，5μg/ml异丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231细胞6h，均可使MMP-9蛋白的表达下降（P＜0.05），P组和S组之间比较，MMP-9蛋白的表达无差异（P＞0.05）。 结论：5μg/ml异丙酚和3.4%V/V七氟烷均能抑制人乳腺癌细胞株MDA-MB-231的侵袭和迁移能力，其机制可能与下调基质金属蛋白酶-9的表达有关，两种药物之间对该癌细胞株的侵袭和迁移能力的影响无差异。
[Abstract]:Objective: breast cancer is one of the most common malignant tumors in women. The incidence of breast cancer is increasing year by year, and the age of breast cancer is getting younger. Metastasis and recurrence are the main causes of death. Human breast cancer cell line MDA-MB-231 is a type of human breast cancer cell. It belongs to three-negative breast cancer, that is, estrogen receptor, progesterone receptor and human epidermal growth factor receptor are all negative breast cancer. The biological characteristics of "Sanyin Breast Cancer" are ductal carcinoma, which is very aggressive, prone to local invasion, distant metastasis and recurrence, and has a younger onset age and poor Nottingham prognostic index (NPI). The first choice of treatment is surgical treatment and chemotherapy. The effect of endocrine therapy and targeted therapy is poor. How to inhibit tumor invasion and metastasis in perioperative period has become the focus of clinical research. Current studies have shown that anesthesia has a certain impact on the invasion and migration of malignant tumors. Propofol and sevoflurane, as common anesthetic drugs, have different effects on the invasion and migration of malignant tumors. However, no studies have been conducted on the effects of propofol and sevoflurane on the invasion and migration of triple negative breast cancer. In this study, we selected human breast cancer cell line MDA-MB-231, to observe the effect of intravenous anesthetic propofol and inhaled anesthetic sevoflurane on their invasion and migration and the possible mechanism. Methods: human breast cancer cell line MDA-MB-231 was inoculated on culture plate for 24 hours. After 24 hours of culture, human breast cancer cell line MDA-MB-231 was randomly divided into three groups: control group (group C), propofol group (P group) and sevoflurane group (S group). All experimental cells were in logarithmic growth stage. The culture plate was placed in a closed aseptic container and in a 37 鈩

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