Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Chen, Kunlun; Zhu, Pengfei; Ye, Jianwen; Yuan, Ling; Du, Zhicheng; Chen, Fangfang; He, Jianxing; Zhang, Shaojin; Zhai, Wenlong

doi:10.7150/jca.32875

Cited by 22 publications

(12 citation statements)

References 27 publications

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“…Matrine could suppress the BrCSCs (breast cancer stem cells) differentiation and self-renewal by downregulating Lin28A expression, leading to the inactivation of Wnt pathway in a Let-7b-dependent way ( Li et al, 2020 ). Oxymatrine could inhibit the invasiveness of HCC by reducing the expression of MMP-2/-9 via inhibiting the activity of p38 signaling pathway ( Chen et al, 2019 ). Meanwhile, Smilacis Glabrae Rhixoma has also been reported to have anti-inflammatory, antiviral, anti-cancer, and immunomodulatory effects ( Jiang and Xu, 2003 ; Ooi et al, 2004 ; Galhena et al, 2012 ; Samarakoon et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

et al. 2021

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Background: Radiation-induced skin injury is a major side-effect observed in cancer patients who received radiotherapy. Thus identifying new radioprotective drugs for prevention or treatment of post-irradiation skin injury should be prompted. A large number of clinical studies have confirmed that Compound Kushen injection (CKI) can enhance efficacy and reduce toxicity of radiotherapy. The aim of this study is to confirm the effect of CKI in alleviating radiotherapy injury in the skin and explore the exact mechanism.Methods: 60 patients who met the inclusion/exclusion criteria were allocated to treatment group (CKI before radiotherapy) or control group (normal saline before radiotherapy) randomly. MTT assay, flow cytometry, Western Blot, and transient transfection were performed to detect the cell viability, cell apoptosis and Bim expression after treatment with CKI or/and radiotherapy.Results: CKI had the effect of alleviating skin injury in cancer patients who received radiotherapy in clinic. CKI induced cancer cell apoptosis when combined with irradiation (IR), while it reversed the induction of cell apoptosis by IR in human skin fibroblast (HSF) cells. And Bim, as a tumor suppressor, was induced in cancer cells but had no change in HSF cells when treated with CKI. Moreover, the above effect could be attenuated when Bim was silenced by siRNA.Conclusion: We conclude that CKI represents a promising radio-protective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) and HSF cells (providing radio-protection via inhibiting IR-induced apoptosis), via regulating Bim. Our study uncovers a novel mechanism by which CKI inhibits human cancer cell while protects skin from radiotherapy, indicating CKI might be a promising radio-protective drug.Clinical Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), identifier ChiCTR2100049164.

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Section: Introductionmentioning

confidence: 99%

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

et al. 2021

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“…However, the understanding of oxymatrine on metastasis is rarely elucidated. Chen et al 28 reported oxymatrine can block the metastasis of hepatocellular carcinoma cells in vitro by reducing p38-mediated MMP-2/-9 expression. Here, not only oxymatrine inhibition of metastasis in colorectal cancer cells, but also the molecular mechanism was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

Li¹,

Sun²,

Xu³

et al. 2020

CMAR

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Background Colorectal cancer (CRC), a type of highly occurred intestinal cancer at present, is prone to metastasis at the later stage of chemotherapy. Looking for the anti-metastatic agents from natural compounds attracted much concern. Here, it aims to demonstrate whether oxymatrine, an anti-cancer natural compound, has anti-metastatic activity and its potential significance in clinic. Materials and Methods Wound healing assay and transwell assay were for evaluating the effect of oxymatrine on cell migration and invasion in vitro. Anti-metastatic action in vivo was determined by hepatic metastasis of colorectal cancer cells in mice. Results Oxymatrine can significantly inhibit cancer cell migration and invasion in vitro. The production of ATP, pyruvate, and lactate was suppressed in CRC cells under the treatment of oxymatrine, as well as the glucose consumption. Meantime, extracellular acidification rates (ECR) were evidently attenuated although the oxygen consumption rates (OCR) were not affected. Both clued that oxymatrine inhibition of metastasis is possibly related to blocking aerobic glycolysis. Subsequent results indicated that pyruvate kinase M2 (PKM2) not hexokinase (HK) and phosphofructokinase (PFK) were involved in oxymatrine blocking glycolysis as the PKM2 kinase activity and expression were inhibited by oxymatrine and the PKM2 activator, TEPP-46, can reverse in part the effect of oxymatrine induced in CRC cells. Furthermore, this process was also mediated by inhibition of glucose transporter 1 (GLUT1). Finally, the in vivo metastatic model in mice showed both 20 mg/kg and 40 mg/kg oxymatrine significantly inhibit liver metastasis of CRC cells in mice, and PKM2 and GLUT1 expression in liver of the oxymatrine-treated group is declined. Conclusion Oxymatrine exerted anti-metastatic activity dependent on inhibition of PKM2-mediated aerobic glycolysis. It is not only an anti-cancer agent but also a potential anti-metastatic compound with clinical application significance.

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“…As overexpression of p38 can increase MMP-9-dependent invasion of pancreatic cells, p38 is one of the target molecules to ameliorate PC [7]. Natural compounds, including silibinin and oxymatrine, have inhibitory effect on MMP-2 and MMP-9 via p38 inactivation in gastric and pancreatic cancer cells [35,36]. In our study, AGE and its effective compound decursin inhibited activation of MMPs by decreasing p38 phosphorylation in PANC-1 and MIA PaCa-2 cells in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Effect of Angelica gigas Nakai Ethanol Extract and Decursin on Human Pancreatic Cancer Cells

et al. 2020

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Pancreatic cancer (PC) is one of the most severe cancers, and its incidence and mortality rates have steadily increased in the past decade. In this study, we demonstrate the effect of Angelica gigas Nakai extract on pancreatic ductal adenocarcinoma cells. We prepared A. gigas Nakai ethanol extract (AGE) using roots of A. gigas Nakai and detected its active compound decursin from AGE by ultra-performance liquid chromatography analysis. AGE and decursin significantly decreased viability and colony formation of PANC-1 and MIA PaCa-2 cells. AGE and decursin induced G0/G1 phase arrest through downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). Caspase-3-dependent apoptosis of PANC-1 cells was promoted by AGE and decursin. Additionally, nontoxic concentrations of AGE and decursin treatment could suppress matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity by inhibiting p38 phosphorylation. Taken together, this study demonstrates that AGE and decursin have potential properties to be considered in PC treatment.

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Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Cited by 22 publications

References 27 publications

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

<p>Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated Aerobic Glycolysis</p>

Effect of Angelica gigas Nakai Ethanol Extract and Decursin on Human Pancreatic Cancer Cells

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