Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro

GAO Mengyuan; GU Jing; LUO Ya1; TANG Qingyun; ZHANG Shengwei; HU Changjiang; OUYANG Qin; YANG Shiming

doi:10.16016/j.1000-5404.202012068

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Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro

更新时间：2021-08-02

- Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro
- Journal of Army Medical University Vol. 43, Issue 9, Pages: 798-805(2021)
- 作者机构：
  
  1. 陆军军医大学（第三军医大学）第二附属医院消化内科
  2. 陆军军医大学（第三军医大学）药学与检验医学系药物化学教研室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202012068
  CLC： R735.2;R965;R977.6
- Published：2021，
  
  Published Online：15 May 2021，
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[1]高梦圆,古晶,罗娅,等.通过下调FOXM1的新型小分子抑制剂1-3-51抗胃癌细胞的作用[J].陆军军医大学学报(原第三军医大学学报),2021,43(09):798-805.GAO Mengyuan,GU Jing,LUO Ya,et al.Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2021,43(09):798-805.

GAO Mengyuan, GU Jing, LUO Ya1, et al. Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro. [J]. Journal of Army Medical University 43(9):798-805(2021)
[1]高梦圆,古晶,罗娅,等.通过下调FOXM1的新型小分子抑制剂1-3-51抗胃癌细胞的作用[J].陆军军医大学学报(原第三军医大学学报),2021,43(09):798-805.GAO Mengyuan,GU Jing,LUO Ya,et al.Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2021,43(09):798-805. DOI： 10.16016/j.1000-5404.202012068.

GAO Mengyuan, GU Jing, LUO Ya1, et al. Anti-gastric cancer effect of a novel small molecule inhibitor 1-3-51 targeting FOXM1 in vitro. [J]. Journal of Army Medical University 43(9):798-805(2021) DOI： 10.16016/j.1000-5404.202012068.

摘要

目的研究新型小分子抑制剂1-3-51在胃癌中调控FOXM1（Forkhead box protein M1）表达及其抗癌的作用。方法CCK-8实验检测1-3-51处理后的BGC823和MKN45细胞IC50；Western blot检测胃癌细胞FOXM1表达；qRT-PCR检测胃癌细胞FOXM1及其下游分子Cyclin D1和MMP9 mRNA表达；流式细胞术测定细胞周期情况；Transwell实验检测胃癌细胞迁移和侵袭能力；裸鼠皮下移植瘤模型检测1-3-51抗胃癌增殖效果；在胃癌细胞BGC823中转染FOXM1 过表达质粒及其空载质粒，CCK-8实验、Transwell实验分别检测1-3-51对胃癌细胞活性、迁移及侵袭等的影响。结果新型小分子抑制剂1-3-51在BGC823和MKN45细胞作用48 h后的IC50分别为(5.429±0.225)μmol/L、(5.169±0.239)μmol/L，并可以显著抑制FOXM1的表达及其下游分子Cyclin D1和MMP9 mRNA表达。1-3-51显著抑制胃癌细胞的增殖、侵袭及迁移。过表达FOXM1后，可部分逆转其抑制细胞增殖、侵袭及迁移能力。结论小分子抑制剂1-3-51在胃癌细胞中可通过抑制FOXM1及其下游分子Cyclin D1和MMP9等的表达，进而降低胃癌细胞增殖、迁移、侵袭能力。

Abstract

ObjectiveTo investigate the role of a novel small molecule inhibitor 1-3-51 in the regulation of FOXM1 expression and its anticancer effect in gastric cancer. MethodsCCK-8 assay was employed to measure the IC50 values in gastric cancer BGC823 and MKN45 cells after 1-3-51 treatment. Western blotting was used to detect FOXM1 expression in the cells. qRT-PCR was adopted to study the mRNA expression of FOXM1 and its downstream target genes Cyclin D1 and MMP9. Flow cytometry and Transwell assay were applied respectively to determine the cell cycle and the migration and invasion of the cells. The anti-proliferation effect of 1-3-51 on gastric cancer was detected in xenograft nude mouse model. FOXM1 overexpression plasmid and the corresponding control vector were transfected into gastric cancer cells BGC823 respectively. CCK-8 assay and Transwell assay were used to detect the changes of 1-3-51 on the activity

migration and invasion of gastric cancer cells. ResultsThe IC50 values of BGC823 and MKN45 cells to 1-3-51 treatment for 48 h was 5.429±0.225 and 5.169±0.239 μmol/L

respectively. And the treatment resulted in significantly decreased expression of FOXM1 and its downstream molecules Cyclin D1 and MMP9. The treatment also significantly suppressed the proliferation

invasion and migration of the gastric cancer cells. Overexpression of FOXM1 partially reversed its abilities to inhibit cell proliferation

invasion and migration. ConclusionOur small molecule inhibitor

1-3-51

can suppress the expression of FOXM1 and its downstream target molecules Cyclin D1 and MMP9 in gastric cancer cells

and thereby reduce the proliferation

migration and invasion abilities of the cells.

关键词

小分子抑制剂FOXM1增殖迁移侵袭胃癌

Keywords

small molecule inhibitorFOXM1proliferationmigrationinvasiongastric cancer

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