石蒜碱抑制胃癌细胞系MGC-803增殖、迁移和侵袭

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1767-1773.

石蒜碱抑制胃癌细胞系MGC-803增殖、迁移和侵袭

鲍美美¹, 徐雯², 王超², 王佳², 苗小芬^2*

1.苏州大学物理科学与技术学院, 江苏苏州 215006;
2.南京中医药大学附属苏州市中医医院病理科,江苏苏州 215009

收稿日期:2021-04-30 修回日期:2021-09-28 发布日期:2021-12-03
通讯作者: *mxf19620319@sohu.com
基金资助:
苏州市中医医院院级课题(2020010)

Lycorine hydrochloride inhibits the proliferation, migration and invasion of gastric cancer cell line MGC-803

BAO Mei-mei¹, XU Wen², WANG Chao², WANG Jia², MIAO Xiao-fen^2*

1. School of Physical Science and Technology, Soochow University, Suzhou 215006;
2. Department of Pathology,Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215009, China

Received:2021-04-30 Revised:2021-09-28 Published:2021-12-03
Contact: *mxf19620319@sohu.com

摘要/Abstract

摘要： 目的探究石蒜碱(LH)对人胃癌细胞系MGC-803细胞增殖、迁移、侵袭的影响及其可能的作用机制。方法 MTT法和集落形成实验检测细胞增殖能力;流式细胞测量术检测细胞周期分布;划痕实验检测细胞迁移能力;Transwell小室法检测细胞侵袭能力; RT-qPCR检测迁移及侵袭相关基因表达。结果 LH对MGC-803细胞活性的抑制呈浓度和时间双重依赖(P＜0.05,P＜0.01),48 h的IC₅₀值为3.76 μmol/L;LH能显著抑制MGC-803细胞的集落形成,在浓度达到20 μmol/L时集落形成受到完全抑制(P＜0.01);LH作用后,将细胞周期阻滞在S期(P＜0.01);随着LH浓度的增加,细胞迁移和侵袭受到明显的抑制(P＜0.01);LH作用后细胞内miR-203基因表达水平上调,而Slug、MMP2、MMP9表达水平下调,并呈浓度依赖性(P＜0.05,P＜0.01)。结论 LH明显抑制MGC-803细胞的增殖,诱导细胞周期阻滞于S期,抑制细胞的迁移和侵袭,上调细胞内miR-203基因表达水平。

关键词: 石蒜碱, 胃癌, 迁移, miR-203, Slug

Abstract: Objective To investigate the effect of lycorine hydrochloride (LH) on the proliferation, migration and invasion of human gastric cancer cell line MGC-803 and its possible mechanism. Methods Cell proliferation ability was detected by MTT assay and colony formation assay. Distribution of cell cycle was detected by flow cytometry. The migration ability of cells was detected by wound healing assay. Transwell assay was used to detect the invasion ability of cells. RT-qPCR was used to detect the effects of LH on gene expression of cell migration and invasion. Results The inhibitory rate of LH on MGC-803 cells was concentration and time dependent (P＜0.05, P＜0.01), and the IC₅₀ value at 48 h was 3.76 μmol/L. The colony formation of MGC-803 cells was significantly inhibited by LH, and the colony formation was completely inhibited when the concentration reached 20 μmol/L (P＜0.01). Cell cycle was arrested in S phase after LH treatment (P＜0.01). With the increase of LH concentration, cell migration and invasion were significantly inhibited (P＜0.01), the expression level of miR-203 gene was up-regulated, while the expression levels of Slug, MMP2 and MMP9 were down-regulated in a concentration-dependent manner (P＜0.05, P＜0.01). Conclusions LH significantly inhibited the proliferation of MGC-803 cells, induced cell cycle arresting in the S phase, and inhibited cell migration and invasion. The expression level of miR-203 gene was up-regulated.

Key words: lycorine hydrochloride, gastric cancer, migration, miR-203, Slug

中图分类号:

鲍美美, 徐雯, 王超, 王佳, 苗小芬. 石蒜碱抑制胃癌细胞系MGC-803增殖、迁移和侵袭[J]. 基础医学与临床, 2021, 41(12): 1767-1773.

BAO Mei-mei, XU Wen, WANG Chao, WANG Jia, MIAO Xiao-fen. Lycorine hydrochloride inhibits the proliferation, migration and invasion of gastric cancer cell line MGC-803[J]. Basic & Clinical Medicine, 2021, 41(12): 1767-1773.

参考文献

[1]Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68: 394-424.
[2]Verma R, Sharma PC. Next generation sequencing-based emerging trends in molecular biology of gastric cancer[J]. Am J Cancer Res, 2018, 8: 207-225.
[3]Nair JJ, van Staden J. Acetylcholinesterase inhibition within the lycorine series of amaryllidaceae alkaloids[J]. Nat Prod Commun, 2012, 7: 959-962.
[4]Zhang WN, Yang JQ, Chen Y, et al. Lycorine hydrochloride suppresses stress-induced premature cellular senescence by stabilizing the genome of human cells[J]. Aging Cell, 2021, 20: 1-13.
[5]Cao ZF, Yu D, Fu SL, et al. Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity[J]. Toxicol Lett, 2013, 218: 174-185.
[6]Li JY, Zhang B, Cui JZ, et al. miR-203 inhibits the invasion and EMT of gastric cancer cells by directly targeting annexin A4[J]. Oncol Res, 2019, 27: 789-799.
[7]Zhang BH, Pan XP, Cobb GP, et al. microRNAs as oncogenes and tumor suppressors[J]. Dev Biol, 2007, 302: 1-12.
[8] Chiang Y, Song Y, Wang Z, et al. Aberrant expression of miR-203 and its clinical significance in gastric and colorectal cancers[J]. J Gastrointest Surg, 2011, 15: 63-70.
[9] Zhou P, Jiang N, Zhang GX, et al. miR-203 inhibits tumor invasion and metastasis in gastric cancer by ATM[J]. Acta Biochim Biophys Sin, 2016, 48: 696-703.
[10]杨屹立, 何学元, 潘新民, 等. miR-205-5p抑制体外胃癌细胞系增殖,迁移和侵袭[J]. 基础医学与临床, 2020, 8: 1068-1075.
[11]Zheng YS, Liu W, Guo LC, et al. The expression level of miR-203 in patients with gastric cancer and its clinical significance[J]. Pathol Res Pract, 2017, 213: 1515-1518.
[12]Yang F, Liu X, Liu Y, et al. miR-181d/MALT1 regula-tory axis attenuates mesenchymal phenotype through NF-κB pathways in glioblastoma[J]. Cancer Lett, 2017, 396: 1-9.
[13]Liu W, Li M, Chen X, et al. microRNA-373 promotes migration and invasion in human esophageal squamous cell carcinoma by inhibiting TIMP3 expression[J]. Am J Cancer Res, 2015, 6: 1-14.
[14]胡灿, 金建伟, 陆仲夏, 等. 血根碱抑制人胃癌SGC-7901细胞增殖、迁移和细胞周期的研究[J]. 中国药理学通报, 2019, 35: 844-849.

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