Abstract: Objective To investigate whether FM19G11 affects the sensitivity of human-derived malignant glioma cell line T98G to temozolomide (TMZ) and underlying molecular mechanisms. Methods T98G cells were treated with 0, 0.5, 1 and 2 μmol/L of FM19G11 and TMZ separately and jointly. The CCK-8 assay and cell clone formation assay were used to detect the proliferation of T98G cells. The Hoechst 33258 staining assay was used to detect the morphological changes of apoptosis in T98G cells. RT-PCR was used to detect the mRNA expression of HIF-1α and its downstream genes VEGF and EPO. Western blot was used to detect the protein level of O⁶-methylguanine-DNA methyltransferase (MGMT), NF-κB P65, HIF-1α,VEGF and EPO. Results Compared with the treatment with TMZ alone, the combined treatment of FM19G11 plus TMZ had a more pronounced effect on the cell proliferation inhibition and morphological changes of apoptosis in T98G cells(P＜0.05). The mRNA and protein of HIF-1α,VEGF and EPO and the protein expression of MGMT, NF-κB P65 were all decreased.(P＜0.05). Conclusions FM19G11 mainly inhibits the expression of HIF-1α, and then down-regulates the expression of MGMT protein, thereby increasing the sensitivity of glioblastoma T98G cells to TMZ. At the same time, FM19G11 also down-regulates genes relating to tumor proliferation and metastasis downstream of HIF-1α and inhibit the NF-κB signaling pathway and then inhibits tumor growth.

Key words: glioblastoma, FM19G11, temozolomide, hypoxia inducible factor 1α, O⁶-methylguanine DNA-methyltransferase