College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Key Laboratory of "Blood Stasis and Toxin" Syndrome of Zhejiang Province, Hangzhou, China.
J Immunol Res. 2022 Feb 8;2022:2619781. doi: 10.1155/2022/2619781. eCollection 2022.
Hepatocellular carcinoma (HCC) is an often-fatal malignant tumor with high lethality. Despite advances and significant efficacy in monotherapy, cancer therapy continues to pose several challenges. Novel combination regimens are an emerging strategy for anti-HCC and have demonstrated to be effective. Here, we propose a potential combination for HCC treatment named arsenic trioxide cooperate cryptotanshinone (ACCS). A remarkable synergistic therapeutic effect has been achieved compared with drugs alone in both in vivo and in vitro experiments. Mechanism study indicated that ACCS exerts its therapeutic actions by regulating macrophage-related immunity and glycolysis. ACCS potentiates the polarization of M1 macrophages and elevates the proportion of M1/M2 to remodel tumor immunity. Further molecular mechanism study revealed that ACCS intensifies the glucose utilization and glycolysis in the macrophage by increasing the phosphorylation of AMPK to activating the AMPK singling pathway. In conclusion, ACCS is a highly potential combination regimen for HCC treatment. The therapeutic potential of ACCS as a candidate option for anticancer drugs in restoring the balance of immunity and metabolism deserves further investigation.
肝细胞癌（HCC）是一种常致命的恶性肿瘤，致死率很高。尽管在单药治疗方面取得了进展和显著疗效，但癌症治疗仍然面临着许多挑战。新型联合治疗方案是抗 HCC 的新兴策略，已被证明是有效的。在这里，我们提出了一种名为三氧化二砷与隐丹参酮（ACCS）的 HCC 治疗潜在联合用药方案。与单独使用药物相比，在体内和体外实验中都取得了显著的协同治疗效果。机制研究表明，ACCS 通过调节巨噬细胞相关免疫和糖酵解发挥其治疗作用。ACCS 增强 M1 巨噬细胞的极化，并提高 M1/M2 的比例，重塑肿瘤免疫。进一步的分子机制研究表明，ACCS 通过增加 AMPK 的磷酸化来增强巨噬细胞中的葡萄糖利用和糖酵解，从而激活 AMPK 信号通路。总之，ACCS 是一种治疗 HCC 的极具潜力的联合治疗方案。ACCS 作为恢复免疫和代谢平衡的抗癌药物候选方案具有很大的治疗潜力，值得进一步研究。
