Chen Yining, Shi Ping, Zhou Suiqing, Yu Kai, Wang Yulang, Yao Feifan, Zhang Ruizhi, Liu Xinyang, Fang Chunyao, Tie Xiaofeng, Li Jun, Xu Jing, Xu Jiali, Pan Xiongxiong
Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Transl Gastroenterol Hepatol. 2025 May 13;10:52. doi: 10.21037/tgh-24-115. eCollection 2025.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumours of the digestive system and the third leading cause of cancer-related deaths worldwide. As the most common type of primary liver cancer, HCC is associated with poor prognosis despite advancements in treatment options such as radical resection, liver transplantation, and adjuvant therapies. Surgical resection remains the cornerstone of HCC treatment; however, postoperative recurrence and metastasis pose significant challenges to patient survival. Intraoperative factors, including immune suppression and the use of certain anaesthetics, have been implicated in tumour cell dissemination and recurrence. While anaesthetic agents like propofol are known to influence tumour cell proliferation, differentiation, and apoptosis. Ciprofol, a novel intravenous anaesthetic, has demonstrated clinical safety and efficacy, but its potential impact on HCC progression and underlying mechanisms requires further exploration. This study aims to explore how ciprofol affects the behaviour of HCC cells and the underlying mechanisms.
Hep3B and HCCLM3 HCC cell lines were treated with varying concentrations of ciprofol. The cell numbers were measured at different time points using the Cell Counting Kit-8 (CCK-8) to find the active concentration. Proliferation was assessed by colony formation and 5-ethynl-2'-deoxyuridine (EdU) assays, whereas invasion and migration were tested using Transwell and wound healing assays. Subcutaneous xenograft and orthotopic liver transplantation models were used to study tumour growth , and a lung metastasis model was created to examine its effects on metastasis. RNA sequencing (RNA-seq) identified transcriptional changes after ciprofol treatment, and western blot and immunofluorescence (IF) validated these findings.
Ciprofol inhibited the proliferation, migration, and invasion of Hep3B and HCCLM3 cells in a manner dependent on both time and dosage. It also reduced tumour growth and lung metastasis in mice. RNA-seq showed that ciprofol affected the MAPK/ERK pathway, which was confirmed by the reduced phosphorylation levels of Raf, MEK, and ERK, without affecting total protein levels.
Ciprofol inhibited the MAPK/ERK pathway by reducing the phosphorylation of Raf, MEK, and ERK, which may explain its inhibitory effects on HCC. The results of this study could guide the use of anaesthetic drugs in HCC surgery.
肝细胞癌（HCC）是消化系统最常见的恶性肿瘤之一，也是全球癌症相关死亡的第三大主要原因。作为原发性肝癌最常见的类型，尽管在根治性切除、肝移植和辅助治疗等治疗选择方面取得了进展，但HCC的预后仍然较差。手术切除仍然是HCC治疗的基石；然而，术后复发和转移对患者生存构成了重大挑战。术中因素，包括免疫抑制和某些麻醉剂的使用，与肿瘤细胞的播散和复发有关。虽然已知丙泊酚等麻醉剂会影响肿瘤细胞的增殖、分化和凋亡。环泊酚是一种新型静脉麻醉剂，已证明其临床安全性和有效性，但其对HCC进展的潜在影响及潜在机制需要进一步探索。本研究旨在探讨环泊酚如何影响HCC细胞的行为及其潜在机制。
用不同浓度的环泊酚处理Hep3B和HCCLM3肝癌细胞系。使用细胞计数试剂盒-8（CCK-8）在不同时间点测量细胞数量以确定活性浓度。通过集落形成和5-乙炔基-2'-脱氧尿苷（EdU）试验评估增殖，而使用Transwell和伤口愈合试验测试侵袭和迁移。采用皮下异种移植和原位肝移植模型研究肿瘤生长，并建立肺转移模型以检查其对转移的影响。RNA测序（RNA-seq）确定环泊酚处理后的转录变化，蛋白质免疫印迹和免疫荧光（IF）验证了这些发现。
环泊酚以时间和剂量依赖性方式抑制Hep3B和HCCLM3细胞的增殖、迁移和侵袭。它还减少了小鼠的肿瘤生长和肺转移。RNA-seq显示环泊酚影响MAPK/ERK通路，Raf、MEK和ERK的磷酸化水平降低证实了这一点，而总蛋白水平不受影响。
环泊酚通过降低Raf、MEK和ERK的磷酸化来抑制MAPK/ERK通路，这可能解释了其对HCC的抑制作用。本研究结果可为HCC手术中麻醉药物的使用提供指导。
