Asiatic Acid Encapsulated Exosomes of Hepatocellular Carcinoma Inhibit Epithelial-Mesenchymal Transition Through Transforming Growth Factor Beta/Smad Signaling Pathway.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in many countries, which accounts for more than 80% of primary liver cancers. Better understanding of the biology of HCC and more therapeutic strategies are urgently needed to improve the current situation. Exosomes, lipid-bound particles derived from cells, have been revealed to play versatile roles in mediating communication between tumor and its microenvironment. Thus, exosomes could act as potential drug delivery systems in cancer treatment. This study aimed to investigate the effect of asiatic acid (AA)-loaded exosomes on the proliferation and migration of HCC cells and clarify the underlying mechanisms. HCC cells were treated with AA-loaded exosomes and cell vitality, migration and invasion were examined. Compared with free AA, AA-loaded exosomes significantly reduced cell vitality, migration, invasion and epithelial mesenchymal transition (EMT). And the inhibition was enhanced as AA concentration went up. Moreover, the expression of proteins involved in EMT and TGF-β/Smad pathway such as TGF-β1, Smad4 and Vimentin were decreased while E-cadherin was up-regulated. Collectively, these findings demonstrate that HCC derived exosomes display as potential drug delivery vehicles in HCC treatment. And AA-loaded exosomes might work by inhibiting EMT through inactivating TGF-β/Smad pathway.