Osteopontin (OPN) is a multi-functional cytokine involved in cell survival, migration and adhesion. Increasing evidence has elucidated its role in tumorigenesis, progression and metastasis. However, the role of OPN in chemoresistance of human hepatocellular carcinoma (HCC) has not yet been clarified. In the present study, we examined the expression of OPN in human HCC samples before and after cisplatin-treatment, the results showed that OPN was significantly increased in cisplatin-resistant specimens. We then studied the effect of cisplatin on OPN expression in HCC cells, after exposure to cisplatin, the expression of OPN in HCC cells was elevated compared to control cells. We also found that PI3K/AKT signaling pathway was also activated by cisplatin and this effect was induced by the OPN pathway. To study the effect of OPN on chemoresistance, HCC cells were treated with cisplatin along with OPN. Incubation with OPN enchanced the chemoresistance of HCC cells to cisplatin. In contrast, blockage of OPN pathway promoted the chemosensitivity of HCC cells to cisplatin. Our results suggest that OPN enhanced chemoresistance of cisplatin in HCC cells by activating PI3K/AKT signaling pathway, blocking the OPN pathway might be a novel way to overcome the disease.

MicroRNAs (miRNAs/miRs) are important molecules that are able to regulate multiple cellular processes in cancer cells. miR-7 has been previously identified as a tumor suppressive miRNA in several types of cancer. The aim of the present study was to investigate whether miR-7 is able to regulate autophagy in hepatocellular carcinoma (HCC) cells. It was identified that miR-7 was significantly downregulated in tumor tissues compared with adjacent normal tissues. Overexpression of miR-7 inhibited cell proliferative activity, which was partially reversed by miR-7 inhibitor. In addition, overexpression of miR-7 significantly induced an increasen in autophagic activity, and luciferase activity assay and western blot analysis identified that mammalian target of rapamycin (mTOR) was a direct target of miR-7. In addition, inhibition of autophagy by 3-methyladenine resulted in a marked enhancement of the proliferation inhibition effect of miR-7. In conclusion, miR-7 was identified to induce proliferation inhibition and autophagy in HCC cells by targeting mTOR, and inhibition of autophagy may be utilized to enhance the antitumor activity of miR-7.

BackgroundThe impact of different anti-virus regimens on prognosis of Chronic hepatitis B (CHB) related cirrhosis remains to be explored. We aim to investigate whether CHB-related HCC patients receiving nucleoside analogue regimen or not have a different prognosis.Methods242 CHB-related compensated cirrhosis patients from 2008 June to 2011 December were included in our study and attributed into groups based on their anti-virus regimens containing adefovir (ADV) or not. The clinical parameters and virological response between ADV-containing regimen group and non-ADV containing regimen groups were reviewed and compared. The risk of hepatocellular carcinoma (HCC) development were analyzed and compared between two groups.Results127 patients received anti-virus regimen containing ADV and 115 patients received anti-virus regimen without ADV. The cumulative risk of HCC development among patients treated with ADV-contained therapy was significantly lower than that observed in patients with non-ADV-contained therapy (p<0.05). Multivariate analysis indicated that ADV-containing regimen treatment was significantly associated with lower probability of HCC development, (hazard ratio, 0.18; 95% confidence interval range, 0.07-0.45, p<0.05).ConclusionBoth anti-virus regimens were effective in reducing serum HBV DNA. Regimen containing ADV decreased the incidence of HCC development in CHB patients with compensated cirrhosis.