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木香烃内酯对人乳腺癌SK-BR-3细胞增殖、迁移和凋亡的影响及

机制研究 Δ

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马 强 1，2＊ ，熊 书 ，苗加伟 ，陈 洁 ，周海英 ，罗 娇 ，杨贞妮 ，孙厚良 ，邓雪松 （1.重庆三峡医药高等
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专科学校基础医学部，重庆 404120；2.重庆市抗肿瘤天然药物工程技术研究中心，重庆 404120；3.重庆三峡
中心医院肾病学科，重庆 404000）
中图分类号 R737.9；R965.2 文献标志码 A 文章编号 1001-0408（2020）11-1342-06
DOI 10.6039/j.issn.1001-0408.2020.11.10
摘 要 目的：研究木香烃内酯对乳腺癌SK-BR-3细胞增殖、迁移和凋亡的影响及机制。方法：取对数生长期的SK-BR-3细胞，分
别加入不同浓度（10、20、30、40、50 μmol/L）的木香烃内酯作用24、48、72 h，采用CCK-8法检测细胞的增殖抑制率。将细胞分为空
白对照组和木香烃内酯10、20、30 μmol/L浓度组，采用Hoechst 33258荧光染色法观察细胞形态及凋亡情况，并计算细胞凋亡率；
采用细胞划痕试验检测细胞的迁移能力，并计算迁移率；采用Western blotting法检测细胞中B淋巴细胞瘤因子2（Bcl-2）、Bcl-2相
关X蛋白（Bax）、半胱氨酸蛋白酶3（Caspase-3）和分裂型Caspase-3（Cleaved Caspase-3）蛋白的相对表达水平。结果：木香烃内酯
对SK-BR-3细胞具有显著的增殖抑制作用（P＜0.05或P＜0.01），且呈现浓度和时间依赖趋势。空白对照组细胞轮廓清晰、形态规
则、贴壁较好；与空白对照组比较，木香烃内酯10、20、30 μmol/L浓度组细胞数量明显减少，细胞结构松散、体积缩小、间隙变大，且
多数细胞轮廓消失、变圆，贴壁不良；细胞迁移率和 Bcl-2 蛋白的相对表达水平均显著降低，细胞凋亡率和 Bax、Caspase-3 及
Cleaved Caspase-3蛋白的相对表达水平均显著升高（P＜0.05或P＜0.01）。结论：木香烃内酯能抑制人乳腺癌SK-BR-3细胞增殖
和迁移，诱导其凋亡，其作用机制可能与上调Bax、Caspase-3和Cleaved Caspase-3表达，下调Bcl-2表达有关。
关键词 木香烃内酯；人乳腺癌SK-BR-3细胞；增殖；迁移；凋亡；机制

Study on the Effects of Costunolide on the Proliferation，Migration and Apoptosis of Human Breast Cancer
SK-BR-3 Cells and Its Mechanism
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MA Qiang ，XIONG Shu ，MIAO Jiawei ，CHEN Jie ，ZHOU Haiying ，LUO Jiao ，YANG Zhenni ，SUN
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Houliang ，DENG Xuesong （1.Dept. of Basic Medicine，Chongqing Three Gorges Medical College，Chongqing
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404120，China；2.Chongqing Engineering Research Center of Antitumor Natural Drugs，Chongqing 404120，
China；3.Dept. of Nephrology，Chongqing Three Gorges Center Hospital，Chongqing 404000，China）
ABSTRACT OBJECTIVE：To study the effects of costunolide on the proliferation，migration and apoptosis of breast cancer
SK-BR-3 cells and its mechanism. METHODS：SK-BR-3 cells in logarithmic growth period were collected and cultured with
different concentrations （10，20，30，40，50 μ mol/L） of costunolide for 24，48，72 h. Inhibitory rate of costunolide on cell
proliferation was detected with CCK-8. The cells were divided into blank control group and costunolide group（10，20，30 μmol/L）.
Hoechst 33258 fluorescence was used to observe the morphology and apoptosis of cells，and apoptotic rate of cells were calculated.
Cell scratch test was used to detect the migration ability of cells and calculate the migration rate. Western blotting was used to
detect the relative expression level of Bcl-2，Bax，Caspase-3 and Cleaved Caspase-3 in cells. RESULTS：The proliferation of
SK-BR-3 cells were significantly inhibited by costunolide（P＜0.05 or P＜0.01），and it shows a trend of concentration and time
dependence. In the blank control group，cells possessed clear contour，regular shape and good adherence. Compared with blank
control group，the number of cells were decreased significantly in 10，20，30 μmol/L costunolide groups，the cell structure was
loose，the volume was reduced，and the gap became larger，and most of the cell contour disappeared and became round，the cell
adherence was poor；cell migration rate and Bcl-2 protein relative expression level were decreased significantly，while apoptosis
rate and the relative expression level of Bax，Caspase-3 and Cleaved Caspase-3 protein were significantly increased（P＜0.05 or
P＜0.01）. CONCLUSIONS： Costunolide can inhibit the
Δ 基金项目：重庆市自然科学基金资助项目（No.cstc2018jcy- proliferation and migration，and induce apoptosis of human
jAX0469）；重庆市教育委员会科学技术研究项目（No.KJ1725385，No.
breast cancer SK-BR-3 cells，mechanism of which may be
KJQN201902701，No.KJQN201802711）；重庆三峡医药高等专科学校
through up-regulating the expression of Bax，Caspase-3 and
校级项目（No.2016xzz03）
＊讲师，硕士。研究方向：抗肿瘤活性药物筛选及应用。电话： Cleaved Caspase-3 while down-regulating the expression of
023-58556816。E-mail：cjmaqiang@163.com Bcl-2.
# 通信作者：副教授，硕士。研究方向：肿瘤发生与防治。电话： KEYWORDS Costunolide；Human breast cancer SK-BR-3
023-58556816。E-mail：71425996@qq.com cells；Proliferation；Migration；Apoptosis；Mechanism

·1342 · China Pharmacy 2020 Vol. 31 No. 11 中国药房 2020年第31卷第11期