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

Abstract

Objective To 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. Methods CCK-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. Results The 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. Conclusion Our 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.

Keywords

• small molecule inhibitor
• foxm1
• proliferation
• migration
• invasion
• gastric cancer