Propofol Suppresses Cell Progression by Inhibiting CCL18 Expression in Hepatoblastoma

Background Propofol is an anesthetic commonly used clinically and has been found to have antitumor activity in various cancers. The purpose of this study was to investigate the role of propofol in hepatoblastoma (HB). Methods CCK-8 and transwell were used to measure cell proliferation, migration, and invasion in HB cells. Cell apoptosis rate was measured by FCM. The expression of CCL18 in HB tissues and cells was detected by RT-qPCR. Western blotting was used to explore the protein expression of CCK18- and PI3K/AKT-related proteins. Results The expression of CCL18 in HB tissues and cells was overexpressed compared with control groups. CCL18 knockdown was found to notably block cell proliferation and progression, while enhancing cell apoptosis in HuH-6 and HepT1 cells. Furthermore, propofol suppressed the proliferation of HB cells in a dose-dependent manner. According to the results, we chose 5 μg/mL of propofol-treated cells for 48 hours as the subsequent experimental conditions. We found that propofol (5 μg/mL, 48 h) significantly blocked cell migration and invasion, but induced cell apoptosis in HuH-6 and HepT1 cells. In addition, CCK18 overexpression facilitated cell progression in HB cells, while propofol dramatically suppressed the effect of CCK18. Besides that, propofol suppressed the PI3K/AKT pathway. Conclusion Propofol suppressed the development of HB cells by inhibiting CCK18 expression and the PI3K/AKT pathway. Therefore, we infer that propofol plays a role in the treatment of HB.

[1]  Y. Nagahara,et al.  BRAP2 inhibits the Ras/Raf/MEK and PI3K/Akt pathways in leukemia cells, thereby inducing apoptosis and inhibiting cell growth. , 2021, Experimental and therapeutic medicine.

[2]  S. Elloumi,et al.  Effect of Compound Propofol Nanoemulsion on Immune Function in Patients with Pancreatic Cancer. , 2021, Journal of Nanoscience and Nanotechnology.

[3]  M. Struys,et al.  Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia. , 2020, British journal of anaesthesia.

[4]  P. Dzięgiel,et al.  CCL18 in the Progression of Cancer , 2020, International journal of molecular sciences.

[5]  T. Kanematsu,et al.  The indirect γ-aminobutyric acid (GABA) receptor agonist gabaculine-induced loss of the righting reflex may inhibit the descending analgesic pathway , 2020, Pharmacology Biochemistry and Behavior.

[6]  Yurong Song,et al.  PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers , 2020, Cell Death & Disease.

[7]  Xiao Jiang,et al.  CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway , 2020, BMC Cancer.

[8]  Yichi Xu,et al.  Effects of propofol on the development of cancer in humans , 2020, Cell proliferation.

[9]  Juan Peng,et al.  Role of PI3K/AKT pathway in cancer: the framework of malignant behavior , 2020, Molecular Biology Reports.

[10]  Yi-long Wu,et al.  Germline variation networks in the PI3K/AKT pathway corresponding to familial high-incidence lung cancer pedigrees , 2020, BMC Cancer.

[11]  R. Alaggio,et al.  Hepatoblastoma and Pediatric Hepatocellular Carcinoma: An Update , 2020, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[12]  Yan Sun,et al.  Propofol exerts anticancer activity on hepatocellular carcinoma cells by raising lncRNA DGCR5 , 2020, Journal of cellular physiology.

[13]  N. Zhang,et al.  Effects of different doses of propofol on the growth and expression of PCNA, CD34 and pAKT proteins in xenografted tumor of BALB/C mice with liver cancer , 2020, Clinical and Translational Oncology.

[14]  Yunfeng Huang,et al.  Propofol Improves Sensitivity of Lung Cancer Cells to Cisplatin and Its Mechanism , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[15]  Xihua Lu,et al.  Effects of propofol on colon cancer metastasis through STAT3/HOTAIR axis by activating WIF‐1 and suppressing Wnt pathway , 2020, Cancer medicine.

[16]  Ling Ye,et al.  Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA-374a/forkhead box O1 signaling axis , 2020, Molecular medicine reports.

[17]  Fang-xiang Zhang,et al.  Propofol affects the growth and metastasis of pancreatic cancer via ADAM8 , 2019, Pharmacological Reports.

[18]  S. Hahn,et al.  Evaluation of the safety of using propofol for paediatric procedural sedation: A systematic review and meta-analysis , 2019, Scientific Reports.

[19]  Yan-tao Fu,et al.  Propofol inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells by downregulating Twist , 2019, Journal of cellular biochemistry.

[20]  G. Zhu,et al.  CCL18 promotes the metastasis of squamous cell carcinoma of the head and neck through MTDH‐NF‐κB signalling pathway , 2019, Journal of cellular and molecular medicine.

[21]  Xiaobin Lv,et al.  Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1 , 2018, Journal of Molecular Medicine.

[22]  Zhenfei Hu,et al.  Propofol Inhibits Proliferation, Migration, Invasion and Promotes Apoptosis Through Down-Regulating miR-374a in Hepatocarcinoma Cell Lines , 2018, Cellular Physiology and Biochemistry.

[23]  Michel M. R. F. Struys,et al.  Clinical Pharmacokinetics and Pharmacodynamics of Propofol , 2018, Clinical Pharmacokinetics.

[24]  M. Buendia,et al.  New insights into diagnosis and therapeutic options for proliferative hepatoblastoma , 2018, Hepatology.

[25]  Weidong Wei,et al.  Efficacy of PI3K/AKT/mTOR pathway inhibitors for the treatment of advanced solid cancers: A literature-based meta-analysis of 46 randomised control trials , 2018, PloS one.

[26]  C. Rancourt,et al.  CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling , 2016, Molecular Cancer.

[27]  Yunjie Zeng,et al.  CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma , 2016, Tumor Biology.

[28]  M. Ling,et al.  The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses , 2015, Molecular Cancer.

[29]  신동훈,et al.  성인에서 발생한 Hepatoblastoma , 1999 .