紫苏醇亚微乳剂对人乳腺癌细胞MDA-MB-435s的增殖抑制作用研究

Resarch on the Anti-proliferative Effect of Perillyl Alcohol of Submicron Emulsion on Human Breast Cancer Cell MDA-MB-435s

目的:探讨紫苏醇亚微乳剂(perillyl alcohol of submicron emulsion,POH-SE)对人乳腺癌细胞MDA-MB-435s的增殖抑制作用及其机制。方法:以紫苏醇溶液(perillyl alcohol,POH-SOL)为对照,不同浓度(0、50、100、200、400及800μmol/L)的POH-SE、紫苏醇壳聚糖亚微乳剂(perillyl alcohol of chitosan submicron emulsion,POH-CSSE)分别作用于细胞;在显微镜下观察细胞形态学变化,采用四甲基偶氮唑盐(MTT)法测其生长抑制率,原位末端标记法(TUNEL)检测细胞凋亡情况,流式细胞术检测细胞生长周期和凋亡率。结果:96 h后,POH-SE组、POH-CSSE组增殖抑制率明显高于POH-SOL组,差异有统计学意义(P<0.01)。随着作用时间的延长,同等药物浓度(800μmol/L)POH-SE组和POH-CSSE组的增殖抑制率均明显高于POH-SOL组,差异均有统计学意义(P<0.01),且POH-CSSE比POH-SE具有更好的抑制作用。不同浓度POH-CSSE和POH-SE均能诱导人乳腺癌MDA-MB-435s细胞凋亡,其中POH-CSSE 200、400及800μmol/L组的凋亡率均明显高于POH-SE组,差异均有统计学意义(P<0.01)。细胞阻滞于G0/G1期,随着POH-SE和POH-CSSE浓度的增加,凋亡细胞增加,呈现剂量依赖模式。结论:POH-SE和POH-CSSE对人乳腺癌细胞MDA-MB-435s的抑制作用较强,其机制可能与其阻断细胞生长周期、诱导细胞凋亡有关。

OBJECTIVE:To probe into the anti-proliferative effect and its mechanism of perillyl alcohol of submicron emulsion(POH-SE)on human breast cancer cell MDA-MB-435s.METHODS:Taking perillyl alcohol solution(POH-SOL)as a control,different concentrations(0,50,100,200,400 and 800μmol/L)of POH-SE,perillyl alcohol of chitosan submicron emulsion(POH-CSSE)acted on the cells respectively;to observe the morphological changes of cells under microscope,use the tetramethyl azozole salt(MTT)method to measure its growth inhibition rate,in situ end labeling(TUNEL)method was used to detect cell apoptosis,flow cytometry was adopted to detect cell growth cycle and apoptosis rate.RESULTS:After 96 h,the proliferation inhibition rate of POH-SE group and POH-CSSE group was significantly higher than that of POH-SOL group,and the difference was statistically significant(P<0.01).With the extension of action time,the proliferation inhibition rate of the POH-SE group and the POH-CSSE group with the same drug concentration(800μmol/L)was significantly higher than that of POH-SOL group,and the differences were statistically significant(P<0.01).Besides,POH-CSSE had better inhibition effect than POH-SE.Different concentrations of POH-CSSE and POH-SE could induce apoptosis of human breast cancer MDA-MB-435s cells,among which the apoptosis rates of 200μmol/L,400μmol/L and 800μmol/L groups in the POH-CSSE group were significantly higher than those in the POH-SE group,and the differences were statistically significant(P<0.01).Cells were blocked at G0/G1 phase,with the increase of concentration of POH-SE and POH-CSSE,the apoptotic cells also increased and showed a dose-dependent pattern.CONCLUSIONS:The inhibitory effects of POH-SE and POH-CSSE on human breast cancer cell MDA-MB-435s are strong,the mechanism may be related to blocking the cell growth cycle and inducing apoptosis.