Sun Pengcheng,Wang Song,Wang Jian,Sun Jing,Peng Min,Shi Ping
Chemerin exhibits a tumor-inhibitory role in hepatocellular carcinoma. However, the effect of chemerin on essential metal elements in hepatic cells remains unclear. In our study, the contents of six important metal ions, including potassium, calcium, sodium, magnesium, iron and zinc, were detected in human hepatoma SMMC7721 and immortal hepatic QSG7701 cells by ICP-AES. The data showed that chemerin only decreases the content of intracellular iron in SMMC7721 cells. The reduction was due to the blockage of iron entry through the decrease in the mRNA levels of divalent metal transporter 1, iron regulatory proteins and transferrin receptors. Furthermore, the reduction of the cellular iron content induced alterations of p53–p27–p21 signaling to arrest the cell cycle at S phase in SMMC7721 cells treated by chemerin. Conversely, iron addition led to recovery from the inhibitory effect of chemerin on SMMC7721 cells. The results suggest that chemerin plays an important role in inhibiting the cell proliferation of hepatocellular carcinomas by interfering with cellular iron homeostasis in this type of tumors.
Ursolic acid (UA), a natural triterpene acid, is a promising anti-cancer drug due to its inhibitory effect on tumor growth and metastasis. However, clinical translation of UA is limited by its poor water solubility and low bioavailability. To overcome these problems, herein an amphiphilic self-assembly nanodrug composed of UA, lactobionic acid (LA) and low-polyamidoamine (low-PAMAM) dendrimers is developed. This near-spherical nanodrug with a uniform size (~180 nm) demonstrated to have an enhanced cytotoxicity against liver cancer SMMC7721 cells, and could attenuate the migration and adhesion of SMMC7721 cells at non-toxic concentrations by suppressing metastasis-related protein MMP-9 expression. Furthermore, in vivo study indicates that the nanodrug exhibited prolonged circulation time in blood as well as increased AUC, MRT and C max , and could effectively inhibit the tumor growth in H22 mice model. Overall, the UA-based nanodrug delivery system reported in the present work represents a novel strategy for targeted tumor therapy.
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