五味子对乳腺癌细胞抑制作用的体外研究

Study of the vitro inhibition effect of Schisandra to breast cancer

目的:评估中药五味子抗癌有效成分木酚素及其代谢产物对雌激素受体阳性以及阴性的乳腺癌细胞株的体外作用,并评价五味子对于乳腺癌的体外杀伤作用。方法:利用ATP生物荧光药物敏感性检测技术(ATP-TCA),检测五味子木酚素对50例乳腺癌的体外杀伤作用,并检测不同浓度五味子木酚素及其代谢物(END、ENL)对于ER(+)的MCF-7、T47D和ER(-)的MDA-MB-231、MDA-MB-435细胞株的杀伤作用。评价五味子的体外作用有效率及其与雌激素受体表型是否相关。结果:五味子对乳腺癌患者的乳腺癌细胞具有明显的体外杀伤作用,体外有效率为34.0%(17/50);五味子木酚素以浓度依赖的方式,显著降低乳腺癌细胞株MCF-7、T47D、MDA-MB-435、MDA-MB-231的存活率,且该抑制作用和细胞雌激素受体的关系并不明显(P>0.05),五味子木酚素在较低浓度(0.1-30μmol/L)下对雌激素受体阳性乳腺癌细胞株MCF-7、T47D表现出促进增殖的作用,当浓度提高至100μmol/L后,五味子木酚素对MCF-7、T47D增殖表现出显著的抑制作用,并呈剂量-效应关系。木酚素的低浓度促进乳腺癌细胞增殖作用在雌激素受体阴性乳腺癌细胞株MDA-MB-435、MDA-MB-231中并不明显,当浓度提高至100μmol/L后,五味子木酚素对MDA-MB-435、MDA-MB-231增殖表现出显著的抑制作用,并呈剂量-效应关系。ENL、END(3-1000μmol/L)在体外对乳腺癌细胞株存在显著抑制作用(P<0.05),并有剂量依赖效应,未发现其与细胞雌激素受体表型有关联(P>0.05)。木酚素在较低浓度区间(0.1-30μmol/L)促进ER(+)细胞株的增殖,但对ER(-)细胞株作用不显著。结论:五味子对乳腺癌细胞系以及乳腺癌患者细胞均具有较强的杀伤作用,值得进一步临床研究和应用。

Objective：To discuss the inhibition effects of Chinese medicine Schisandra and its metabolites on ER （ ＋ ） and ER （ - ） breast cancer cells in vitro, to explore the function of Schisandra on preventing breast cancer. Methods： The tumor cells of 50 patients with breast cancer were treated by Schisandra lignans. Human breast cancer cells MCF - 7,T47 D, MDA - MB - 231, MDA - MB - 435 were treated with lignans, END, ENL and tested by ATP - TCA assay, to evaluate the inhibitive effect of lignans and its metabolins on breast cancer cell lines, and to analyze the relation between this function and estrogen receptor. Results： Breast cancer patients who treated with Schisandra~ cells have significant effective cytotoxicity in vitro ,which rate was 34.0% （17/50）. The survival rates of breast cancer cell lines were significantly reduced by ENL, END in dose - dependent effect. There was no significant difference among these groups （P 〉 0.05 ）. LIGNANS promoted proliferation of estrogen receptor - positive breast cancer cell lines at lower concentrations, however, the survival rates of estrogen receptor- negative breast cancer cell lines were not pro- moted by LIGNANS at lower concentrations. When the concentration increased to 100 p^mol/L, LIGNANS showed sig- nificantly inhibitive effect on all the cell lines in concentration - dependent manner. Conclusion ： Schisandra lignans can effectively prevent and reduce the occurrence of breast cancer. The results may be of reference value for screening effective population and preventing breast cancer by lignans.