Bruceine D and Afatinib Combination Inhibits Ovarian Cancer Cells Proliferation and Migration Through DNA Damage Repair and EGFR Pathway
Abstract Owing to the high rates of relapse and migration, ovarian cancer has been recognized as the most lethal gynecological malignancy worldwide. The activity of the EGFR signaling pathway is frequently associated with ovarian cancer cell proliferation and migration. Despite this knowledge, inhibition of EGFR signaling in ovarian cancer patients failed to achieve satisfactory therapeutic effects. In this study, we identified that Bruceine D and EGFR inhibitor, afatinib, combination resulted in synergistic anti- ovarian cancer effects. The results indicated that compared with one of both drugs alone, the combination of Bruceine D and afatinib slowed the DNA replication rate, inhibition of cell viability, and proliferation and clone formation. This resulted in cell cycle arrest and cell apoptosis. In addition, the combination of Bruceine D and afatinib possessed a stronger ability to inhibit the ovarian cancer cell adhesion and migration than treatment with Bruceine D or afatinib alone. Mechanistically, the combined treatment triggered intense DNA damage, suppressed DNA damage repair, and enhanced the inhibition of the EGFR pathway. These results demonstrated that compared with each pathway inhibition, combined blocking of both DNA damage repair and the EGFR pathway appears to more effective against ovarian cancer treatment. The results support the potential of Bruceine D and afatinib combination as a therapeutic strategy for ovarian cancer patients.