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不同麻醉藥對人乳腺癌細(xì)胞侵襲與遷移能力的影響

發(fā)布時間:2018-10-31 16:05
【摘要】:目的:乳腺癌是女性最常見的惡性腫瘤之一,其發(fā)病率呈逐年上升趨勢,且發(fā)病年齡逐漸年輕化,術(shù)后轉(zhuǎn)移和復(fù)發(fā)是其最主要的死亡原因。人乳腺癌細(xì)胞株MDA-MB-231是人乳腺癌細(xì)胞的一種分型,屬于三陰乳腺癌,即雌激素受體、孕激素受體以及人表皮生長因子受體均為陰性的乳腺癌!叭幦橄侔鄙飳W(xué)特征為導(dǎo)管癌,腫瘤侵襲性很強(qiáng),,易發(fā)生局部侵襲、遠(yuǎn)處轉(zhuǎn)移和復(fù)發(fā),且發(fā)病年齡較小,Nottingham預(yù)后指數(shù)(NPI)差,其治療方法首選手術(shù)治療和化療,對內(nèi)分泌治療以及靶向治療效果較差。針對此類患者,在圍術(shù)期如何抑制腫瘤的侵襲與轉(zhuǎn)移已成為目前臨床研究的重點,F(xiàn)階段研究表明,麻醉對惡性腫瘤侵襲和遷移有一定的影響。作為臨床常用的麻醉藥物異丙酚和七氟烷,相關(guān)研究顯示二者對惡性腫瘤侵襲和遷移的影響不同。但對于“三陰乳腺癌”,異丙酚和七氟烷對其侵襲和遷移的影響如何,尚無相關(guān)研究。本研究選取人乳腺癌細(xì)胞株MDA-MB-231,觀察靜脈麻醉藥異丙酚和吸入麻醉藥七氟烷對其侵襲和遷移能力的影響以及可能的機(jī)制。 方法:人乳腺癌細(xì)胞株MDA-MB-231接種于培養(yǎng)板,培養(yǎng)24h后,隨機(jī)將其分為3組:對照組(C組)、異丙酚組(P組)、七氟烷組(S組)。所有實驗用細(xì)胞均處于對數(shù)生長期。將培養(yǎng)板置于無菌密閉容器內(nèi),置于37℃恒溫水浴鍋中。密閉容器進(jìn)氣口連接麻醉機(jī),出氣口連接麻醉氣體監(jiān)測儀。對照組通入95%O2-5%CO2混合氣體1L/min,孵育6h;異丙酚組加入5μg/ml異丙酚,同時通入95%O2-5%CO2混合氣體1L/min,孵育6h;七氟烷組通入95%O2-5%CO2混合氣體1L/min和3.4%V/V七氟烷,孵育6h;每組細(xì)胞處理完畢后,放回37℃、5%CO2培養(yǎng)箱中,培養(yǎng)24h,備用。采用Transwell侵襲實驗法檢測細(xì)胞的侵襲能力,采用細(xì)胞劃痕實驗法檢測細(xì)胞的遷移運動能力,采用Western blot法檢測基質(zhì)金屬蛋白酶-9(MMP-9)的表達(dá)。 結(jié)果:Transwell侵襲實驗結(jié)果顯示,與C組相比,5μg/ml異丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231細(xì)胞6h,穿過Transwell小室的細(xì)胞數(shù)均減少(P<0.05)。P組和S組之間比較,穿過Transwell小室的細(xì)胞數(shù)無差別(P>0.05)。 細(xì)胞劃痕實驗結(jié)果顯示,與C組相比,5μg/ml異丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231細(xì)胞6h,均可使該細(xì)胞的遷移率降低(P<0.05),P組與S組之間比較,細(xì)胞遷移率差異無統(tǒng)計學(xué)意義(P>0.05)。 Western blot實驗結(jié)果示,與C組相比,5μg/ml異丙酚和3.4%V/V七氟烷作用于人乳腺癌MDA-MB-231細(xì)胞6h,均可使MMP-9蛋白的表達(dá)下降(P<0.05),P組和S組之間比較,MMP-9蛋白的表達(dá)無差異(P>0.05)。 結(jié)論:5μg/ml異丙酚和3.4%V/V七氟烷均能抑制人乳腺癌細(xì)胞株MDA-MB-231的侵襲和遷移能力,其機(jī)制可能與下調(diào)基質(zhì)金屬蛋白酶-9的表達(dá)有關(guān),兩種藥物之間對該癌細(xì)胞株的侵襲和遷移能力的影響無差異。
[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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