GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway

TL;DR

This study shows that high levels of GFPT2 make ovarian cancer cells resistant to paclitaxel by activating the NF-κB pathway.

Contribution

The study identifies GFPT2 as a novel mediator of paclitaxel resistance in epithelial ovarian cancer via NF-κB signaling.

Findings

High GFPT2 expression correlates with paclitaxel resistance in ovarian cancer cells.

GFPT2 knockdown increases drug sensitivity, while overexpression reduces it.

GFPT2 promotes resistance by activating the NF-κB signaling pathway.

Abstract

This study investigated the role of glutamine-fructose-6-phosphate transaminase 2 (GFPT2) in the response of epithelial ovarian cancer cells to paclitaxel, a standard chemotherapy drug. We analyzed GFPT2 expression across various EOC cell lines, including SKOV3, HEY, ES-2, A2780, and OVCR3. In HEY cell lines, we performed GFPT2 knockdown, while A2780 cells were engineered for GFPT2 overexpression. Following these manipulations, we assessed the cellular responses to paclitaxel treatment. Results demonstrated a correlation between GFPT2 levels and paclitaxel resistance; those with high GFPT2 (SKOV3 and HEY) expression were less sensitive compared to the cells with low GFPT2 expression (A2780). Downregulating GFPT2 enhanced drug sensitivity in HEY cells, whereas its overexpression impaired drug sensitivity in A2780 cells. Mechanistically, GFPT2’s role in facilitating paclitaxel resistance was linked to the activation of the nuclear factor-κB (NF-κB) signaling pathway, possibly influenced by NK3 Homeobox 2. Our findings suggest that GFPT2 is a critical mediator of paclitaxel resistance through NF-κB pathway activation in EOC, providing potential targets for improving therapeutic efficacy against this challenging malignancy.

Figures