A Traditional Chinese Remedy for Hepatocellular Carcinoma Functions by Suppressing Exosomal miR-23a-3p/Smad Signaling

Abstract

A decoction of Jianpi Huayu (JHP) has been used traditionally in orthodox Chinese medicine to treat tumors such as hepatocellular carcinoma (HCC), however, the mechanism is still a mystery. Intercellular communication in the cancer cell microenvironment points toward a strong role of exosomes, but their contribution to HCC is still not well understood. Xie and colleagues investigated the anti-neoplastic effects of JHD and the possible function of exosomal signaling. Nude mice models with subcutaneous cancer were used to gauge the effects of JHD. Migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) of cultured HCC cells were mitigated by JHD. From the EMT-induced HCC cells, exosomes increased the invasion, migration, and EMT of other cultured HCC cells, whereas post-treatment of JHD, exosomes from EMT-induced HCC cells had little effect. Exosomal miR-23a-3p which is significantly upregulated in cancer cells as compared to normal cells was reduced in JHD-treated cultured HCC cells. Post hepatectomy, patients with high miR-23a-3p levels had low survival rates. Smad signaling protein expression as well HCC cell proliferation was upregulated by miR-23a-3p. More critically, miR-23a-3p overexpression countered the EMT and Smad signaling inhibition brought about by JHD treatment. In vivo examinations revealed that treatment with JHD additionally diminished the development of HCC-derived tumors in naked mice, and decreased the levels of miR-23a-3p in serum exosomes and the degree of EMT in cancer cells. The authors conclude that the anticancer properties of JHD partially if not completely are due to the downregulation of exosome-mediated intercellular miR-23a-3p transfer and subsequent blockade of Smad signaling. Disrupting this exosomal miR-23a-3p/Smad signaling pathway may be an effective treatment. J Ethnopharmacol. 2022 Aug 10;294:115360.