Yixiong Wang1, Baozhu Xu2, Jianying Zhou1, Xianyan Wu1. 1. Department of Anesthesiology, The Quanzhou First Affiliated Hospital of Fujian Medical University, Quanzhou, China. 2. Department of Radiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal malignant tumor with a poor prognosis, and is the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the anti-tumor effect of propofol on the proliferation, apoptosis, and cell cycle of HCC by regulating adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. METHODS: The cell counting Kit-8 (CCK-8) assay was employed to screen the effect of propofol on HepG2 cell viability at various concentrations (0.3, 0.6, 1.2, 2.5, 5, 10, 20, 40, 80 and 160 µM). We selected propofol at concentrations of 5, 10 and 20 µM for subsequent experiments. Flow cytometry was used to examine the apoptosis and cell cycle of HCC. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure the messenger ribonucleic acid (mRNA) expression levels of proliferating cell nuclear antigen (PCNA) and survivin. Western blotting was applied to measure the protein expression levels of PCNA, survivin, cleaved caspase-3, cleaved caspase-9, p27 (Kip1), and cyclin A. The effects of propofol were evaluated by establishing a xenograft tumor model. RESULTS: After treatment with propofol, the mRNA expression levels of PCNA and survivin were decreased compared with the 0 µM propofol (control) group. The colony formation assay showed that the colony formation rate was obviously down-regulated. Flow cytometry demonstrated that HepG2 cell apoptosis was increased. G0/G1 was enhanced compared with the control group, while G2/M was restrained. The levels of cleaved caspase-3, cleaved caspase-9, p27, phospho-AMP-activated protein kinase α1 (p-AMPKα1), phospho-mammalian target of rapamycin (p-mTOR), and phospho-Unc-51 like autophagy activating kinase 1 (p-ULK1) were notably elevated, while the levels of cyclin A were suppressed. The xenograft tumor volume declined in vivo compared with the HepG2 xenograft group. The expression levels of cell proliferation markers (PCNA) were significantly down-regulated markedly, while the expression levels of cell cycle markers (p27) were notablyup-regulated. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining showed that cell apoptosis was increased. The levels of p-AMPKα1 were also up-regulated. CONCLUSIONS: Propofol inhibits the proliferation, apoptosis, and cell cycle of HCC by regulating AMPK in vivo and in vitro. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal malignant tumor with a poor prognosis, and is the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the anti-tumor effect of propofol on the proliferation, apoptosis, and cell cycle of HCC by regulating adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. METHODS: The cell counting Kit-8 (CCK-8) assay was employed to screen the effect of propofol on HepG2 cell viability at various concentrations (0.3, 0.6, 1.2, 2.5, 5, 10, 20, 40, 80 and 160 µM). We selected propofol at concentrations of 5, 10 and 20 µM for subsequent experiments. Flow cytometry was used to examine the apoptosis and cell cycle of HCC. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure the messenger ribonucleic acid (mRNA) expression levels of proliferating cell nuclear antigen (PCNA) and survivin. Western blotting was applied to measure the protein expression levels of PCNA, survivin, cleaved caspase-3, cleaved caspase-9, p27 (Kip1), and cyclin A. The effects of propofol were evaluated by establishing a xenograft tumor model. RESULTS: After treatment with propofol, the mRNA expression levels of PCNA and survivin were decreased compared with the 0 µM propofol (control) group. The colony formation assay showed that the colony formation rate was obviously down-regulated. Flow cytometry demonstrated that HepG2 cell apoptosis was increased. G0/G1 was enhanced compared with the control group, while G2/M was restrained. The levels of cleaved caspase-3, cleaved caspase-9, p27, phospho-AMP-activated protein kinase α1 (p-AMPKα1), phospho-mammalian target of rapamycin (p-mTOR), and phospho-Unc-51 like autophagy activating kinase 1 (p-ULK1) were notably elevated, while the levels of cyclin A were suppressed. The xenograft tumor volume declined in vivo compared with the HepG2 xenograft group. The expression levels of cell proliferation markers (PCNA) were significantly down-regulated markedly, while the expression levels of cell cycle markers (p27) were notablyup-regulated. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining showed that cell apoptosis was increased. The levels of p-AMPKα1 were also up-regulated. CONCLUSIONS: Propofol inhibits the proliferation, apoptosis, and cell cycle of HCC by regulating AMPK in vivo and in vitro. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Huajun Zhao; Yuan-Hung Lo; Li Ma; Susan E Waltz; Jerilyn K Gray; Mien-Chie Hung; Shao-Chun Wang Journal: Mol Cancer Ther Date: 2011-01 Impact factor: 6.261
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