摘要
目的探究血根碱对胃癌细胞增殖、侵袭及细胞周期的影响机制。方法采用MTT法检测血根碱(3、6、9μmol·L^(-1))对胃癌SGC-7901细胞活性的抑制作用;划痕法和流式细胞术检测血根碱对细胞的迁移和周期的影响; Western blot法检测迁移及细胞周期相关蛋白MMP-2、MMP-9、cyclin D1、CDK4及p16的蛋白表达水平。结果与空白对照组相比,不同浓度的血根碱作用24 h后,随着药物浓度的增加,细胞活性明显降低,分别为82. 6%、63. 1%、46. 5%,有显著性差异(P <0. 05);流式细胞术结果显示,与空白对照组相比,血根碱(3、6、9μmol·L^(-1))处理胃癌细胞后,处于G1期的细胞比例明显升高(P <0. 05);划痕结果显示,与空白对照组相比,血根碱处理后胃癌细胞的迁移能力明显降低;血根碱作用后,MMP-2、MMP-9、cyclin D1、CDK4的蛋白表达量明显下调(P <0. 05),p16的蛋白表达量明显上调(P <0. 05)。结论血根碱在体外明显抑制SGC-7901细胞增殖,降低细胞的迁移能力,诱导细胞在G1期阻滞,其抗胃癌作用与其调控MMP-2、MMP-9、cyclin D1、CDK4及p16的蛋白表达有关。
Aim To explore the mechanism of the effects of sanguinarine on the proliferation, invasion and cell cycle of gastric cancer cells. Methods MTT assay was used to detect the inhibitory effect of sanguinarine(3, 6, 9 μmol·L^-1 ) on the cell viability of gastric cancer SGC-7901 cells. Wound healing and flow cytometry were applied to detect cell migration and cell cycle respectively. Western blot was employed to determine the protein expression levels of migration and cell cycle related proteins MMP-2, MMP-9, cyclin D1, CDK4, and p16. Results Compared with control group, the cell viability decreased significantly with the increase of drug concentration after 24 h treatment( P <0.05). Flow cytometry results showed that the proportion of cells in G1 phase after treatment with 3, 6, 9 μmol·L ^-1 of sanguinarine significantly increased( P <0.05). Wound healing results indicated that the migration ability of gastric cancer cells was significantly inhibited after sanguinarine treatment. After sanguinarine treatment, the protein expression levels of MMP-2, MMP-9, cyclin D1 and CDK4 were significantly down-regulated( P <0.05), whereas the protein expression level of p16 was significantly up-regulated( P <0.05). Conclusions Sanguinarine significantly inhibits the proliferation, reduces the migration ability of cells, induces cell arrest in G1 phase, and its anti-cancer effect is related to its regulation of MMP-2, MMP-9, cyclin D1, CDK4 and p16.
作者
胡灿
金建伟
陆仲夏
徐志远
倪益秀
吕航
汪丽菁
程向东
HU Can;JIN Jian-wei;LU Zhong-xia;XU Zhi-yuan;NI Yi-xiu;LYU Hang;WANG Li-jing;CHENG Xiang-dong(The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China;Dept of Abdominal Surgical, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China;School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266100, China;Dept of Ultrasonics, Zhejiang Cancer Hospital, Hangzhou 310022, China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第6期844-849,共6页
Chinese Pharmacological Bulletin
基金
浙江省中医药科技计划重点研究项目(No 2016ZZ012)
浙江省自然科学基金资助项目(No LY16H280011
LY18H290006)
浙江省医药卫生科技项目(No WKJ-ZJ-1728)
浙江省分析测试和实验动物计划项目(No2018C37045)
关键词
血根碱
SGC-7901
胃癌
细胞迁移
细胞周期
中药
sanguinarine
SGC-7901
gastric cancer
cell migration
cell cycle
traditional Chinese medicine
