Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9

Liu,Jie; Wen,Xiaojun; Liu,Bin; Zhang,Qingyu; Zhang,Jingjing; Miao,Huilai; Zhu,Runzhi

doi:10.3892/mmr.2016.4872

Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9

Authors:
- Jie Liu
- Xiaojun Wen
- Bin Liu
- Qingyu Zhang
- Jingjing Zhang
- Huilai Miao
- Runzhi Zhu
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Affiliations: Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, Guangdong 524001, P.R. China
Published online on: February 5, 2016 https://doi.org/10.3892/mmr.2016.4872
Pages: 2401-2408
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant types of tumor worldwide with a high rate of mortality. Diosmetin (DIOS) exhibits various activities, including anticancer activities. However, the role of DIOS in the metastasis of HCC, and its underlying molecular mechanism, remain to be fully elucidated. In the present study, the antimetastatic effects of DIOS were investigated in SK‑HEP‑1 and MHcc97H HCC cell lines. Cell proliferation, wound healing, motility, invasion and adhesion capacities were examined to evaluate the inhibitory effect of DIOS on the metastasis of HCC cells. Cell viability was detected using an MTT assay in order to verify the inhibitory effect of DIOS on the proliferation of HCC cells. Cell migration was assessed using would healing and motility assays in order to verify the inhibitory effect of DIOS on the migration of HCC cells. Cell invasion and adhesion assays were performed in order to verify the inhibitory effect of DIOS on the invasion and adhesion of HCC cells. Matrix metalloproteinase (MMP)‑2/9, proteins of the mitogen‑activated protein kinase (MAPK) pathway (c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase and p38 MAPK) and protein kinase C‑δ were detected in order to verify the potential molecular mechanisms of DIOS in the inhibition of the metastasis of HCC cells. DIOS was observed to inhibit the metastasis of SK‑HEP‑1 and MHcc97H cells by downregulating the expression of MMP‑2/9 via the PKC/MAPK/MMP pathways. DIOS also inhibited the migration and invasion of the HCC cells, and may serve as a potential candidate agent for the prevention of HCC metastasis.

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