Role of GPX4 inhibition-mediated ferroptosis in the chemoresistance of ovarian cancer to Taxol in vitro.

BACKGROUND: Ovarian cancer remains a common gynecological tumor and the fifth leading cause of death worldwide. Taxol-based chemotherapy is a standard approach to the treatment of ovarian cancer. Glutathione peroxidase 4 (GPX4) is the key regulator of ferroptosis, which is an important form of cell death. Here, we investigate the effect of GPX4 inhibition-mediated ferroptosis on the sensitivity of ovarian cancer cells to Taxol. METHODS AND RESULTS: A2780/PTX and OVCAR-3/PTX Taxol-resistant ovarian cancer cells were established, and stable GPX4 knockout cell lines were generated via lentivirus GPX4-sgRNA. The GPX4 expression level, the apoptosis rate and cell viability were analyzed. The levels of ferroptosis-related factor indicators such as malondialdehyde (MDA) and reactive oxygen species (ROS) were measured. The results showed that the GPX4 protein and mRNA levels were increased in the Taxol-resistant cells. Moreover, GPX4 knockout reduced cell viability and inhibited the colony formation rate. In addition, we found that GPX4 inhibition increased Taxol sensitivity by inducing ferroptosis. CONCLUSIONS: In summary, our studies reveal that GPX4 inhibition promotes ferroptosis and increases the sensitivity of ovarian cancer cells to Taxol in vitro.