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Cancer stem cells (CSCs) have been reported to be associated with the recurrence and drug resistance of liver cancer. In the present study, stem cell-like HepG2 cell spheres were enriched using stem cell conditioned culture medium. As expected, stem-like HepG2 cell spheres exhibited increased resistance to sorafenib. Metformin, a common drug used to treat type 2 diabetes mellitus, reduced the diameters and numbers of stem-like HepG2 spheres, and increased their sensitivity to sorafenib. Western blotting confirmed that low doses of metformin reversed the epithelial-mesenchymal transformation (EMT) process of HepG2 spheres. These results suggested that metformin enhanced sensitivity to sorafenib, which was probably through reversal of the EMT process of sphere-forming cells and by reducing the formation of CSCs. [ABSTRACT FROM AUTHOR]

Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-me thoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells. The proportion of GD-induced CD3+CD56+ CIK and CD3-CD56+ NK cells was ~4% higher respectively compared with the control. Notably, combination therapy with CIK/NK cells stimulated by GD, markedly suppressed the proliferation of the chronic myelogenous leukemia K562 cell line. Following GD treatment, the cytotoxicity improved by ~25 and 21% when the effector/target ratio was 20:1 and 10:1, respectively. The results of the present study suggested a novel protocol for CIK/NK cell proliferation and revealed that GD may serve as a potent innate and adaptive immunomodulator in immunocyte culture. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury is a major challenge influencing the outcomes of hepatic transplantation. Transforming growth factor-β (TGF-β) and its downstream gene, SMAD family member 3 (Smad3), have been implicated in the pathogenesis of chronic hepatic injuries, such as hepatic fibrosis. Thus, the present study aimed to investigate the role of the TGF-β/Smad3 signaling pathway on hepatic injury induced by IR in vivo. In total, 20 129S2/SvPasCrl wild-type (WT) mice were randomized into two groups; 10 mice underwent IR injury surgery and 10 mice were sham-operated. Histopathological changes in liver tissues and serum levels of alanine aminotransferase (ALT) were examined to confirm hepatic injury caused by IR surgery. The expression levels of TGF-β1, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected via western blotting. Furthermore, a total of five Smad3−/− 129S2/SvPasCrl mice (Smad3−/− mice) and 10 Smad3+/+ littermates received IR surgery, while another five Smad3−/− mice and 10 Smad3+/+ littermates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflammatory cell infiltration after IR were evaluated in the liver tissues of Smad3−/− mice and Smad3+/+ mice. The results demonstrated that the expression levels of TGF-β1, Smad3 and p-Smad3 were elevated in hepatic tissue from WT mice after IR injury. Aggravated hepatic injury, increased apoptosis and enhanced inflammatory cell infiltration induced by hepatic IR injury were observed in the Smad3−/− mice compared with in Smad3+/+ mice. Collectively, the current findings suggested that activation of the TGF-β/Smad3 signaling pathway was present alongside the hepatic injury induced by IR. However, the TGF-β/Smad3 signaling pathway may have an effect on protecting against liver tissue damage caused by IR injury in vivo. [ABSTRACT FROM AUTHOR]