Fedratinib inhibits ovarian cancer progression by downregulating QPCT expression.

OBJECTIVE

Among gynecological malignant tumors, ovarian cancer is one of the most common, and the death rate is the highest. However, most ovarian cancer patients will be resistant to the application of Olaparib. Searching for novel therapeutic agents and targets for ovarian cancer is crucial.

METHODS

In order to study the effect of Fedratinib on ovarian cancer cells, we used CCK-8, scratch assay, Transwell assay, cell cycle assay and Immunohistochemical detection. To explore the regulatory impact of Fedratinib on QPCT gene, we have included Western blotting, Rescue experiment, and other methods.

RESULTS

In this study, we screened Fedratinib, a Janus kinase 2 inhibitor, a drug candidate for ovarian cancer using bioinformatics combined with cellular assays. Fedratinib had a significant impact on the proliferation of ovarian cancer cells, and the potential target of Fedratinib might be QPCT. The expression of QPCT was significantly elevated in ovarian cancer tissue samples and ovarian cancer cells, and cell proliferation, migration, and invasion were enhanced by the overexpression of QPCT. However, the expression of QPCT was significantly downregulated in the cells after treatment with Fedratinib, and cell viability induced by knockdown of QPCT decline can be reversed by Ferroptosis inhibitors and Necroptosis inhibitors.

CONCLUSIONS

Fedratinib suppresses QPCT expression, which might associated with inhibition of JAK-STAT signaling, thus inhibiting the growth of ovarian cancer cells through Ferroptosis or Necroptosis.