Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo

Abstract Aim Cisplatin‐based chemotherapy is the first‐line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment or serious side effects often occurs in ovarian cancer, and thus, there is an urgent need for effective and combined therapies to overcome such obstacles. In the present study, we aimed to uncover synergistic effects between erastin and cisplatin (CDDP) in inhibiting ovarian cancer cell growth by inducing ferroptosis in vitro and in vivo. Methods We performed a CCK‐8 assay to detect cell viability in response to erastin alone or in combination with cisplatin and provided further confirmation by western blotting analysis. Transmission electron microscopy and flow cytometry analysis were used to depict the characteristics of ferroptosis. In addition, an ovarian cancer tumor xenograft was built to verify the effects in vivo. Results CDDP induced multiple modes of cell death‐including ferroptosis in ovarian cancer cell lines. Mechanistically, erastin triggered ferroptosis and increased the levels of reactive oxygen species (ROS) so as to augment the cytotoxic effect of cisplatin. Combination therapy based on CDDP and erastin appeared to maximize the therapeutic effects while minimizing side effects in ovarian cancer both in vitro and in vivo. Conclusion Collectively, our results indicate that erastin works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS‐mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.