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. 2019 Aug 29;10(22):5397-5403.
doi: 10.7150/jca.32875. eCollection 2019.

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

Kunlun Chen  1 , Pengfei Zhu  1 , Jianwen Ye  1 , Yuan Liao  1 , Zhicheng Du  1 , Fangfang Chen  2 , He Juanjuan  3 , Shaojin Zhang  4 , Wenlong Zhai  1
Affiliations

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

Kunlun Chen et al. J Cancer. .

Abstract

As one of the major alkaloid components in Sophoraflavescensait (kushen), oxymatrine has been used widely across the world in anti-inflammatory and anti-cancer therapies. However, the effect in the metastasis of hepatocellular carcinoma (HCC) and related mechanism(s) are still unclear. The present study aimed to investigate the anti-metastatic effect of oxymatrine on HCC cells. Oxymatrine could also inhibit the protein levels of MMP-2/-9 in a dose-dependent relationship. Moreover, oxymatrine reduces the activity of p38 signaling pathway via inhibiting the phosphorylation of p38. The inhibition effect of oxymatrine on the expression of MMP-2/-9 and the phosphorylated of p38 was also detected in vivo. Combined treatment with p38 signaling pathway inhibitor and oxymatrine may have a synergistic effect on MMP-2/-9 and invasion of HCC cells. Therefore, oxymatrine may have inhibited GBC invasiveness by reducing the expression of MMP-2/-9 via inhibiting the activity of p38 signaling pathway. As a potentially novel therapeutic drug, oxymatrine may play an important role in the treatment of HCC.

Keywords: hepatocellular carcinoma; matrix metalloproteinase; migration and invasion; oxymatrine; p38 signaling pathway.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Oxymatrine reduces the cellular viability of HepG2, MHCC97H and SMMC7721 cells.
Figure 2
Figure 2
Anti-metastatic effects of oxymatrine in MHCC97H cells. (A) For the migration assay, MHCC97H cells were pre-incubated with various concentrations of oxymatrine (0, 0.1, 0.2 and 0.3 mg/ml) and analyzed. (B) The percent invasion rate was expressed as a percentage of the control (0 mg/ml). (C) For the invasion assay, MHCC97H cells were pre-incubated with various concentrations of oxymatrine (0, 0.1, 0.2 and 0.3 mg/ml) and analyzed. (D) The percent invasion rate was expressed as a percentage of the control (0 mg/ml). Cell spontaneous invasion in DMSO was designated as control. Values represent the means ± SD of three independent experiments. *p< 0.05 and **p< 0.01 vs control group.
Figure 3
Figure 3
Oxymatrine suppresses the expression of MMP-2 /-9 and activity of p38 signaling pathway in MHCC97H cells.
Figure 4
Figure 4
Effects of the p38 inhibitor SB203580 and oxymatrine on cell invasion and MMP-2/-9 expression in MHCC97H cells. (A) MHCC97H cells were pretreated with SB203580 and then incubated in the presence or absence of oxymatrine (0.1 mg/ml) for 24 h. Cellular invasiveness was measured using the transwell chamber invasion assay. (B) The percent invasion rate was expressed as a percentage of control. (C, D) The protein levels of MMP-2/-9 in MHCC97H cells treated with various concentrations of oxymatrine (0, 0.1, 0.2 and 0.3 mg/ml) and analyzed with western blotting. Values represent the means ± SD of three independent experiments. *p< 0.05 and **p< 0.01 vs control group.
Figure 5
Figure 5
Oxymatrine inhibits the growth of tumor in MHCC97H xenografts. (A) Growth curves presented the volumes of tumor in BALB/c nude mice treated with PBS or oxymatrine. (B) The weight of tumor was measured in each group when the experiment was over. (C)The expression level of MMP-2 and MMP-9 in tumor tissues was detected by western blot. (D) The expression level of p38 and p-p38 in tumor tissues was detected by western blot. *P<0.05 vs PBS (control). PBS, phosphate-buffered saline.
Figure 6
Figure 6
Oxymatrine inhibits the invasion of HepG2 and SMMC7721 cells.
See this image and copyright information in PMC

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