Downregulation of acetyl-CoA carboxylase induces ferroptosis and inhibits tumor growth in oral squamous cell carcinoma.

Abstract

In this study, we aimed to investigate the specific role of the acetyl-CoA carboxylase (ACACA) gene in oral squamous cell carcinoma (OSCC). We constructed the human tongue carcinoma cell line SAS with low ACACA expression and evaluated changes in cell proliferation, apoptosis, and ferroptosis. Then, the effect of combined treatment with cisplatin and ferroptosis inducer erastin was measured. To assess the impact of ACACA expression on tumor growth in vivo, we established xenograft models with varying ACACA levels in twelve male BALB/c nude mice. ACACA knockdown significantly reduced the proliferation ability of SAS cells, and increased the number of apoptotic cells. ACACA knockdown also induces ferroptosis, and this effect was enhanced by combined treatment with cisplatin and erastin. In vivo experiments demonstrated lower tumor volume and weight in the ACACA knockdown group than those in the control group. Exploring the combined effect of ACACA knockdown and cisplatin treatment revealed a promising synergistic effect against ferroptosis signaling and downstream signaling pathways in SAS cells and in vivo. These findings suggest that targeting the ACACA gene has the potential to be a novel therapeutic strategy for oral cancer treatment.