Effect of the MGMT inhibitor Diethylamyne nonoate on epithelial mesenchymal transition in glioblastoma

Glioblastoma is the most aggressive and malignant (grade IV) brain tumor. Glioblastoma shows resistance to current therapeutic approaches, resulting in a poor prognosis. The primary cause of chemotherapeutic resistance in glioblastoma is the MGMT protein. Enhancement of the success of TMZ-based alkylating therapy is expected with MGMT inhibition. Diethylenetriamine NONOate (DEA/NO) is an MGMT inhibitor capable of releasing nitric oxide (NO). It is indicated that NO may affect the growth, invasion, differentiation, and therapeutic resistance of glioma cells. One of the cellular events contributing to therapeutic resistance in glioblastoma is Epithelial-to-Mesenchymal Transition (EMT). The effect of DEA/NO on the EMT pathway in cancer cells is unknown. This thesis aims to investigate the effect of DEA/NO on the expression of genes involved in the EMT process in glioblastoma cells. For this purpose, T98G and U-87 MG cell lines were used. The cytotoxicity of DEA/NO in glioma cells was determined using MTT assay, and its effect on cell migration was determined using wound healing assay. The effect of DEA/NO on the expression of genes involved in the EMT pathway was detected by qRT-PCR. IBM SPSS Version 20.0 was used for data analysis. According to the cytotoxicity results, the U-87 MG cell line was found to be more sensitive than T98G. The effect of DEA/NO on cell migration was found to be higher in the U87-MG cell line compared to the T98G cell line. DEA/NO significantly reduced the expression of EMT genes in both T98G and U-87 MG cell lines (p<0.05). DEA/NO does not induce EMT in glioma cells and may have the potential to be used in combination with chemotherapeutic drugs by reducing the expression of EMT genes. Our study is the first in the literature to investigate the effects of DEA/NO on the expression of genes involved in the EMT process.