Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu Province, China.
Cancer Lett. 2023 Jan 1;552:215970. doi: 10.1016/j.canlet.2022.215970. Epub 2022 Oct 17.
Hepatocellular carcinoma (HCC) is a leading malignancy of the digestive system, especially in China. Although radiotherapy, chemotherapy, and transarterial chemoembolization have achieved tremendous success, surgical resection remains the primary treatment for HCC patients. Recent studies have shown that intravenous anesthetic drugs may affect the malignant behaviors of tumor cells, ultimately leading to differences in the postoperative prognosis of patients. Etomidate is one of the most widely used intravenous anesthetic drugs for the induction and maintenance of anesthesia in tumor patients undergoing surgery. However, the effects and underlying mechanisms of etomidate on HCC cells have not yet been characterized. Our study indicated that etomidate significantly impedes the malignant progression of HCC cells. Mechanistically, etomidate inhibits phosphorylation and, ultimately, the activity of Janus kinase 2 (JAK2) by competing with ATP for binding to the ATP-binding pocket of JAK2. Thus, it suppresses the JAK2/STAT3 signaling pathway in HCC cells to exert its anti-tumor efficacy. Herein, we provide preclinical evidence that etomidate is the optimal choice for surgical treatment of HCC patients.
肝细胞癌（HCC）是消化系统的主要恶性肿瘤，尤其是在中国。尽管放疗、化疗和经动脉化疗栓塞已取得巨大成功，但手术切除仍然是 HCC 患者的主要治疗方法。最近的研究表明，静脉麻醉药物可能会影响肿瘤细胞的恶性行为，最终导致手术肿瘤患者的术后预后存在差异。依托咪酯是用于诱导和维持手术肿瘤患者麻醉的最广泛使用的静脉麻醉药物之一。然而，依托咪酯对 HCC 细胞的作用及其潜在机制尚未得到描述。我们的研究表明，依托咪酯可显著阻碍 HCC 细胞的恶性进展。在机制上，依托咪酯通过与 ATP 竞争结合 JAK2 的 ATP 结合口袋来抑制 JAK2 的磷酸化，最终抑制 JAK2 的活性。因此，它通过抑制 HCC 细胞中的 JAK2/STAT3 信号通路发挥其抗肿瘤功效。在此，我们提供了依托咪酯是 HCC 患者手术治疗的最佳选择的临床前证据。
