Hypoglycemic Agents Increase Regulatory Factor X1 to Inhibit Cancer Cell Behaviour in Human Glioblastoma Cells.

Glioblastoma multiforme is a deadly brain tumour in humans. We have shown that regulatory factor X1 (RFX1), a transcription factor, inhibits the proliferation, migration and invasion of human glioblastoma cells. This study was designed to identify the existing medications that could increase RFX1 in human glioblastoma cells and to determine whether these medications could inhibit the cancer cell behaviours. A bioinformatics approach was used to identify the medications that increased RFX1. The effects of these medications on human glioblastoma cell proliferation, migration and invasion were assayed under cell culture and mouse brain xenograft conditions. Pioglitazone, rosiglitazone and WY-14643 increased RFX1 based on bioinformatics prediction and Western blotting data. These hypoglycemic agents reduced the proliferation, migration and invasion of human glioblastoma cell cultures. These agents reduced metalloproteinase 2 (MMP2) activity in the culture medium. Silencing RFX1 attenuated hypoglycemic agent-induced inhibition of cancer cell behaviours and MMP2 activity. Pioglitazone reduced the xenograft tumour volume and migration distance of U87 human glioblastoma cells in the mouse brain. RFX1-siRNA attenuated these effects. Our results provide additional evidence for RFX1 as a therapeutic target for human glioblastoma and suggest that pioglitazone, rosiglitazone and WY-14643 inhibit cancer cell behaviour of human glioblastoma cells via upregulating RFX1.