PDK1/AKT signaling is involved in the anti-tumor effect of gramine and cisplatin chemoresistance in ovarian cancer cells

Abstract

Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, with limited therapeutic options and poor long-term prognosis. Gramine, an indole alkaloid predominantly derived from the rhizomes of Arundo donax L., has demonstrated antitumor activity in various cancer types; however, its effects and mechanistic basis in OC have not been systematically investigated. In the present study, the biological activity of gramine in OC cells were evaluated using cell counting kit-8, colony formation and EdU assays for proliferation; TUNEL staining for apoptosis; and wound healing and Transwell assays for migration and invasion. Western blotting was performed to examine underlying molecular changes. The present results showed that gramine significantly suppressed OC cell proliferation, migration and invasion, while promoting cell apoptosis. Mechanistically, gramine reduced PDK1 protein levels, and enforced PDK1 overexpression largely reversed the suppressive effects of gramine on malignant phenotypes. Consistently, PDK1 restoration also attenuated gramine-induced downregulation of phosphorylated AKT. Furthermore, gramine enhanced the sensitivity of OC cells to cisplatin, an effect associated with PDK1/AKT signaling inhibition. Collectively, these findings suggest that gramine inhibits malignant progression and attenuates cisplatin resistance in OC cells, at least in part, through blockade of the PDK1/AKT pathway. Although limited to in vitro models, this work provides preliminary evidence supporting further exploration of gramine as a potential research tool or lead compound in OC.