Evaluation of therapeutic effects of KC7F2, temozolomide, and its combination on genes involved in the Wnt signal pathway in the U87MG glioma cell line

Abstract Glioma is the most common malignant primary brain tumor that survives less than 12 months after diagnosis. The Wnt signaling pathway creates a complex network of proteins that have different effects on cells, so they can be involved in many cancers, including gliomas. Drug resistance is seen in many cancer treatments. Therefore, we investigated the combined effect of Temozolomide (TMZ) and KC7F2 on cell survival and changes in gene expression in the Wnt signal pathway. The effects of TMZ and KC7F2 on cancer cell viability and proliferation were investigated by WST-1 method. Isobologram analysis was performed to evaluate the combined effects of TMZ and KC7F on U87MG glioma cell line. Also, Quantitative RT-PCR was used to evaluate the mRNA expression level of genes related to the Wnt signal pathway in treated cancer cells and control groups. IC50 TMZ and KC7F2 values in U87MG cell lines were determined to be 461µM and 19µM in 48 hours, respectively. Combined effects of TMZ and KC7F2 on the U87MG cell line show the CI values for TMZ and KC7F2 were found as 0.746. It was found that KC7F2+TMZ increased APC, CCND1, CXXC4, DAAM1, FBXW11, FRZB, FZD3, FZD8, LEF1, LRP5, LRP6, PYGO1, RHOA, RHOU, RUVBL1, VANGL2, WIF1, WNT10A, WNT16, WNT3A, and WNT6 while decreasing NKD1, PRICKLE1, DKK1, WNT1 expressions in U87MG cell lines. The results show that the combination of TMZ and KC7F2 can be a promising anti-cancer agent for the treatment of glioblastoma through the Wnt / β-catenin signaling pathway. However, further studies are needed to understand all angles.