The combination of Angelica sinensis polysaccharide and cisplatin promotes ferroptosis in cisplatin-resistant ovarian cancer cells by regulating GPX4, thereby reversing their resistance to cisplatin

Abstract

Abstract Background Angelica sinensis (Oliv.) Diels has been used for centuries in Chinese traditional medicine to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis, can inhibit various forms of cancer. Nevertheless, the therapeutic potential of ASP for treating ovarian cancer remains largely unexplored. Methods The study investigated cell proliferation and invasion, as well as the effects of a combination of ASP and DDP after tumor formation in nude mice. Tumor size was monitored, and HE staining was conducted on tissue samples. The identification of key gene GPX4 was performed via RNA-seq and bioinformatic analysis. GPX4 was overexpressed using lentivirus transfection, and its expression was evaluated via RT-qPCR and western blot. Additionally, the ferroptosis of cells was assessed through the measurement of Fe2+, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Results The results indicated a synergistic effect of ASP combined with DDP, leading to better inhibition of proliferation and invasion of SKOV3/DDP cells. Similarly, ASP combined with DDP demonstrated tumor proliferation inhibition in tumor-forming nude mice, while maintaining good safety. Bioinformatics analysis of 843 differentially expressed genes (DEGs) revealed that the key gene GPX4 played a significant role in the mechanism of action. Furthermore, the expression of GPX4 was inhibited by ASP combined with DDP, which resulted in SKOV3/DDP inhibition of proliferation and invasion. The study also demonstrated that ASP combined with DDP led to increased levels of Fe2+ and MDA, while decreasing levels of GSH and SOD, suggesting the promotion ferroptosis of SKOV3/DDP cells. Conclusions The combination of ASP and DDP has the ability to inhibit the proliferation and invasion of SKOV3/DDP cells. Additionally, inhibiting GPX4 expression in SKOV3/DDP cells promotes ferroptosis.