Effect of lupeol on invasion and metastasis of human hepatoma HepG2 and SK-HEP-1 cells and its mechanism.
10.19540/j.cnki.cjcmm.20200901.403
- Author:
Bo-Jia LIU
1
;
Qing NING
2
;
Rong-Ling ZHONG
2
;
Zhi XIA
2
;
Zi-Yu JIANG
2
;
Jie SONG
1
;
Ying-Jie WEI
1
Author Information
1. Third School of Clinical Medical of Nanjing University of Chinese Medicine Nanjing 210028, China Key Laboratory of Traditional Chinese Medicine Drug Release System, State Administration of Traditional Chinese Medicine, Jiangsu Provincial Academy of Chinese Medicine Nanjing 210028, China.
2. Key Laboratory of Traditional Chinese Medicine Drug Release System, State Administration of Traditional Chinese Medicine, Jiangsu Provincial Academy of Chinese Medicine Nanjing 210028, China.
- Publication Type:Journal Article
- Keywords:
EMT;
HepG2 cell;
SK-HEP-1 cell;
hepatocellular carcinoma cells;
invasion;
lupeol;
metastasis
- MeSH:
Animals;
Carcinoma, Hepatocellular;
Cell Line, Tumor;
Cell Movement;
Epithelial-Mesenchymal Transition;
Gene Expression Regulation, Neoplastic;
Hep G2 Cells;
Humans;
Liver Neoplasms;
Matrix Metalloproteinase 2/metabolism*;
Mice;
Mice, Nude;
Neoplasm Invasiveness;
Pentacyclic Triterpenes
- From:
China Journal of Chinese Materia Medica
2020;45(24):6028-6035
- CountryChina
- Language:Chinese
-
Abstract:
Epithelial-mesenchymal transformation(EMT) exists in embryonic development and is closely related to cell migration and invasion. The increased EMT level in tumors showed that E-cadherin was replaced by N-cadherin, and the expression of interstitial markers such as α-SMA and vimentin was up-regulated. It has been reported that lupeol can reduce the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9) and N-cadherin to inhibit the metastasis of osteoma cells. However lupeol has been less studied in liver cancer. Therefore, this paper investigated the effect of lupanol on invasion and metastasis of human hepatoma cell line HepG2 and SK-HEP-1 and its possible mechanism. MTT assay and Annexin V/PI double staining were used to investigate the effect of lupeol on activity and apoptosis of HepG2 cells and SK-HEP-1 cells. Moreover, the effect of lupeol on the invasion of HepG2 cells and SK-HEP-1 cells were evaluated by Transwell assay. The expressions of E-cadherin, N-cadherin, α-SMA, vimentin and MMP-9 were measured by Western blot. The model of subcutaneous transplantation of nude mice and the lung metastasis model of H22 hepatocellular carcinoma cells were established to evaluate the efficacy of lupeol in vivo on tumor growth and lung metastasis by HE staining combined with immunohistochemical assay. The results showed that lupeol inhibited the activity and invasion of HepG2 cells and SK-HEP-1 cells in a dose-dependent manner and induced apoptosis. Western blot showed that the expression of E-cadherin, a landmark protein for EMT, was induced by lupeol, and the expressions of N-cadherin, α-SMA, vimentin and MMP-9 were decreased. In vivo experiments showed that lupeol inhibited tumor growth in mice bearing xenograft. In addition, immunohistochemical experiments confirmed that lupeol could up-regulate the expression of E-cadherin in tumor tissues of nude mice, reduce the expression of N-cadherin, and inhibit the metastasis of liver cancer H22 cells in the lungs of mice. The above results indicated that the mechanism of lupeol inhibiting the invasion and metastasis of HCC cells may be related to the regulation of EMT process.
