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The cross-talk between hepatocellular carcinoma (HCC) cells and activated hepatic stellate cells (HSCs) is considered to be important for modulating the biological behavior of tumor cells. However, the molecular links between inflammation and cancer in the activation of HSCs remain to be elucidated. The present study demonstrated that cluster of differentiation (CD)147 is a key molecule involved in the interaction between HCC cells and HSCs. The effects of conditioned medium from human HCC cells on the activation of the human HSC line, LX-2, were assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting, RT-qPCR and gelatin zymography were also used to investigate the effects of CD147 on the activation of LX-2. The expression levels of α-smooth muscle actin (α-SMA) and CD147 were assessed in a co-culture system of LX-2 and FHCC-98 cells by immunofluorescence staining and immunoblotting. In hepatic tissues from a rat model of fibrosis, immunohistochemistry and immunoblotting were performed to detect the expression levels of α-SMA and CD147. Tumor-conditioned medium and CD147 promoted cell proliferation, activated LX-2 cells, increased the expression levels of α-SMA, collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1), and increased the secretion of matrix metalloproteinase (MMP)-2. The HSCs, which were induced in the co-culture system of HCC cells and HSCs exhibited marked expression levels of CD147. In the hepatic tissue of rat models of fibrosis induced by CCl4, marked expression levels of CD147 were observed in the activated HSCs. Therefore, CD147 promoted the activation of HSCs and was a key molecule during HCC cell-HSC cross-talk in the rat liver. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies and accounts for ~6% of all types of human cancer worldwide, particularly in Asia. The incidence and mortality rates in the USA have also rapidly increased. Saikosaponin-d (SSD), a saponin derivative extracted from several species of Bupleurum (Umbelliferae), possesses unique biological activities, including anti-inflammatory, antihepatitic and immunomodulatory effects. Our previous studies have demonstrated that SSD inhibits the proliferation and induces the apoptosis of HCC SMMC-7721 cells by downregulating the expression of cyclooxygenase (COX)-2 and decreasing the production of prostaglandin E2. However, the specific mechanism underlying how SSD controls the expression of COX-2 remains to be elucidated. In the present study, it was demonstrated that hypoxia inducible factor-1α (HIF-1α) was responsible for the expression of COX-2 under hypoxic conditions in HCC cells, and the activation of signal transducer and activator of transcription 3 (STAT3) was required for the expression of HIF-1α. SSD treatment inhibited STAT3 activation [phosphorylation of STAT3 (p-STAT3)], reduced the protein level of HIF-1α and decreased the expression of COX-2. These results suggested that SSD may target HCC cells by suppressing the expression of COX-2 through the p-STAT3/HIF-1α pathway. [ABSTRACT FROM AUTHOR]