Indirubin inhibits cervical cancer by inhibiting apoptosis and autophagy through the PI3K/AKT and MAPK pathways

This study investigated the effects of indirubin on autophagy and apoptosis in cervical cancer models, with a focus on elucidating the underlying molecular mechanisms. A xenograft tumor model in BALB/c-Nude mice and in vitro experiments using HeLa cell lines were employed. Indirubin treatment demonstrated concentration-dependent inhibition of cervical cancer cell growth, accompanied by induction of apoptosis and autophagy. Mechanistic analysis revealed that indirubin exerted its effects through dual modulation of the PI3K/AKT signaling axis. It enhanced autophagic flux, as evidenced by increased LC3-II/LC3-I ratio and decreased P62 expression. Concurrently, indirubin induced mitochondrial apoptosis through upregulation of pro-apoptotic Bax expression and downregulation of anti-apoptotic Bcl-2 levels. These coordinated molecular alterations ultimately led to programmed cell death execution. Additionally, indirubin inhibited the activation of the MEKK1/SEK1/JNK/AP-1 signaling pathway, further contributing to its anti-tumor effects. These findings suggest that indirubin inhibits cervical cancer cell growth by regulating the PI3K/AKT pathway, enhancing autophagy, and promoting apoptosis, providing a theoretical basis for its therapeutic potential in cervical cancer treatment.