Shan Weiran, Zuo Kendrick, Zuo Zhiyi
Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
Kenneth P. Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Cell Mol Med. 2024 Dec;28(23):e70260. doi: 10.1111/jcmm.70260.
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.
多形性胶质母细胞瘤是一种致命的人类脑肿瘤。我们已经表明，转录因子调控因子X1（RFX1）可抑制人胶质母细胞瘤细胞的增殖、迁移和侵袭。本研究旨在确定能够增加人胶质母细胞瘤细胞中RFX1的现有药物，并确定这些药物是否能抑制癌细胞行为。采用生物信息学方法来识别可增加RFX1的药物。在细胞培养和小鼠脑异种移植条件下，检测这些药物对人胶质母细胞瘤细胞增殖、迁移和侵袭的影响。基于生物信息学预测和蛋白质印迹数据，吡格列酮、罗格列酮和WY-14643可增加RFX1。这些降糖药物减少了人胶质母细胞瘤细胞培养物的增殖、迁移和侵袭。这些药物降低了培养基中金属蛋白酶2（MMP2）的活性。沉默RFX1减弱了降糖药物诱导的对癌细胞行为和MMP2活性的抑制作用。吡格列酮减少了小鼠脑中U87人胶质母细胞瘤细胞的异种移植肿瘤体积和迁移距离。RFX1小干扰RNA减弱了这些作用。我们的结果为RFX1作为人胶质母细胞瘤的治疗靶点提供了更多证据，并表明吡格列酮、罗格列酮和WY-14643通过上调RFX1来抑制人胶质母细胞瘤细胞的癌细胞行为。
