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 Liao¹, Zhicheng Du¹, Fangfang Chen², He Juanjuan³, Shaojin Zhang⁴, Wenlong Zhai^1✉

1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, P.R. China
2. Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
3. Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
4. Department of Ueology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P.R. China
^*Contributed equally

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Citation:
Chen K, Zhu P, Ye J, Liao Y, Du Z, Chen F, Juanjuan H, Zhang S, Zhai W. Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway. J Cancer 2019; 10(22):5397-5403. doi:10.7150/jca.32875. Available from https://www.jcancer.org/v10p5397.htm

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: oxymatrine, hepatocellular carcinoma, migration and invasion, matrix metalloproteinase, p38 signaling pathway