HDACi induces apoptosis of osteosarcoma cells by inhibiting the MAPK pathway

Investigate the malignant biological effects of the histone deacetylase inhibitor (HDACi) in osteosarcoma (OS) and study the underlying mechanisms through mRNA sequencing. CCK-8, colony formation, Transwell assays, live/dead staining, and flow cytometry were used to observe the malignant biological effects of 4-phenylbutyric acid (4-PA) on OS cells. mRNA sequencing revealed the mechanism of action of 4-PA on OS cells. Western blotting (WB) was used to detect changes in the expression of histone acetylation, apoptosis, and MAPK-related proteins in OS cells treated with 4-PA. Flow cytometry was used to examine the number of apoptotic OS cells after 4-PA intervention. Animal experiments were conducted to validate the effects of 4-PA on OS cells in vivo. Intervention with 4-PA can significantly inhibit the activity, invasion, migration, and colony-forming abilities of OS cells, while promoting cell death and cell cycle arrest. Results from flow cytometry and apoptosis-related protein detection suggest that 4-PA has the ability to induce apoptosis in OS cells. mRNA sequencing and Western blot analyses showed that 4-PA can inhibit the MAPK/ERK pathway in OS cells. Rescue experiments indicated that the promotion of apoptosis in OS cells by 4-PA may be achieved through the inhibition of the MAPK/ERK pathway. In vivo experiments further confirmed the inhibitory effect of 4-PA on OS growth and its ability to promote apoptosis. The results suggest that HDACi can significantly inhibit the malignant biological abilities of OS cells and induce apoptosis in OS cells by suppressing the MAPK/ERK pathway.