Suppression of NANOG Expression Reduces Drug Resistance of Cancer Stem Cells in Glioblastoma

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that harbors therapy-resistant cancer stem cells (CSCs). Due to the limited effectiveness of conventional chemotherapies and radiation treatments against CSCs, there is a critical need for the development of innovative therapeutic approaches. Our previous research revealed the significant expression of embryonic stemness genes, NANOG and OCT4, in CSCs, suggesting their role in enhancing cancer-specific stemness and drug resistance. In our current study, we employed RNA interference (RNAi) to suppress the expression of these genes and observed an increased susceptibility of CSCs to the anticancer drug, temozolomide (TMZ). Suppression of NANOG expression induced cell cycle arrest in CSCs, specifically in the G0 phase, and it concomitantly decreased the expression of PDK1. Since PDK1 activates the PI3K/AKT pathway to promote cell proliferation and survival, our findings suggest that NANOG contributes to chemotherapy resistance in CSCs through PI3K/AKT pathway activation. Therefore, the combination of TMZ treatment with RNAi targeting NANOG holds promise as a therapeutic strategy for GBM.

Automated summary

Glioblastoma (GBM) is a brain tumor that is difficult to treat due to therapy-resistant cancer stem cells (CSCs). In this study, the researchers used RNA interference to suppress the expression of NANOG and OCT4 genes in CSCs, which increased their susceptibility to the anticancer drug temozolomide (TMZ). The researchers found that suppression of NANOG expression resulted in cell cycle arrest and decreased expression of PDK1, suggesting that NANOG contributes to chemotherapy resistance in CSCs through activation of the PI3K/AKT pathway.