Magnesium Ions Promote the Apoptosis of Cervical Cancer Cells through the PI3K/AKT/FoxO1 Pathway

As we know, Cervical cancer is one of the leading causes of mortality among women worldwide. Magnesium ions (Mg²⁺) are intricately involved in virtually all biological processes, demonstrating antitumor properties. However, the pathways through which Mg²⁺ mediates its antitumor activity in cervical carcinoma require further clarification. This research investigated the effects of varying Mg²⁺ levels on the growth and programmed cell death of cervical cancer cells (SiHa and HeLa). Mg²⁺ effectively suppressed cellular proliferation, migration, and invasive capacity, and induced the proportion of the G0/G1 phase. Meanwhile, Apoptosis was also promoted in cervical cancer cell lines following Mg²⁺ exposure, proceeding through mitochondrial dysfunction characterized by an elevated Bax/Bcl-2 ratio, reduced membrane potential, cytochrome c leakage, and caspase-3 activation. Significant downregulation of phosphorylated PI3K, AKT, and FoxO1 following Mg²⁺ treatment was observed, while PI3K activator administration attenuated Mg²⁺-induced apoptosis. Mg²⁺-mediated suppression of HeLa xenograft tumor growth in nude mice was demonstrated, with immunohistochemical confirmation of elevated TdT-mediated dUTP Nick-End Labeling(TUNEL) and cleaved caspase-3 expression. These results suggest that Mg²⁺, which was highly concentrated in the region, exerts its anti-cervical cancer function through downregulation of the PI3K/AKT/FoxO1 pathway, which offers a novel method and mechanism to therapeutic strategies for managing cervical cancer.