Glioblastoma is one of the most common and invasive types of primary brain malignancies in adults, accounting for 45.5% of malignancies. Its annual prevalence is low compared to other cancers. The survival rate of this disease is about 14 months after diagnosis. Temozolomide (TMZ) is a common chemotherapy drug used to treatment of glioblastoma, but drug resistance against this drug is an important barrier to successful treatment of this cancer. Today, siRNAs play a signifcant role in cancer treatment. SIX4 is a transcriptional regulatory molecule that can act as a transcriptional suppressor and an activator in target genes involved in diferentiation, migration, and cell survival processes. The aim of this study was to evaluate the efect of SIX4-siRNA on A-172 glioblastoma cells, its role as a tumor suppressor, and its combination with TMZ. We studied the cytotoxic efect of the SIX4-siRNA and TMZ on A-172 cells using the MTT assay investigated their efect on apoptosis and cell cycle of A-172 cells used wound healing assays to assess their efect on cell migration. Finally, we used qRT-PCR to study the mRNA expression levels of genes involved in apoptosis and migration of tumoral cells after treatments. Based on our results, silencing SIX4-siRNA expression reduced the cell viability of A-172 cells and sensitize these cells to TMZ. Furthermore, we observed an increase in apoptosis and cell cycle arrest, and a decrease in migration. Bax and caspase-9 overexpression and BCL2 and MMP9 downregulation were detected in the combination of SIX4-siRNA and TMZ. According to our results, the combination of SIX4-siRNA and TMZ can be a very useful strategy for successful glioblastoma treatment
