Ardipusilloside inhibits survival, invasion and metastasis of human hepatocellular carcinoma cells

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• 作者：Lianqing Lou^a ; ^{minggao.zhao@yahoo.com} ; Weiwei Ye^a ; Yongxin Chen^a ; Shuang Wu^a ; Linzheng Jin^a ; Jinke He^a ; Xingfei Tao^a ; Jinghong Zhu^a ; Xiangyi Chen^a ; Anmei Deng^b ; ¹ ; Jinhe Wang^a ; ¹
• 关键词：MMP2 ; matrix metalloproteinase 2 ; MMP9 ; matrix metalloproteinase 9 ; Mek ; mitogen-activated protein kinase kinase ; Erk ; extracellular signal-regulated kinases ; Rac1 ; Ras-related C3 botulinum toxin substrate 1 ; Cdec42 ; cell division control protein 42 homol
• 刊名：Phytomedicine
• 出版年：2012
• 期刊代码：259_09447113
• 类别：med
• 出版时间：15 May, 2012
• 卷：19
• 期：7
• 页码：603-608
• 文件大小：558 K

摘要

Ethnopharmacological relevance

Ardipusilloside I is a triterpene-saponin isolated from the Traditional Chinese Medicine Ardisia pusilla A. DC. Its effects and mechanism on invasion and metastasis of liver cancer cells are unclear.

Materials and methods

The human hepatocellular carcinoma cell line HepG2 and SMMC-7721 cells were treated with different doses of Ardipusilloside I. Cellular survival, in vitro migration and invasion were evaluated. In vivo metastatic abilities of the HCC cells were detected. We further investigated expression and phosphorylation of Mek, Erk and Akt by using Western blot. MMP2 and MMP9 activities were evaluated by gelatin zymography. E-cadherin expression, Rac1 and Cdc42 activities were examined by Western blot and pull-down assay.

Results

Ardipusilloside I inhibited invasion and metastasis of HCC cells both in vitro and in vivo by reducing the protein expressions of metalloproteinase (MMP)-9 and MMP2 proteins. Ardipusilloside I activated Rac1 that enhanced E-cadherin activity and resulted in significantly less metastasis.

Conclusion

Our findings indicate that Ardipusilloside I has the potential of inhibition of liver cancer survival, invasion and metastasis both in vitro and in vivo.