No abstract

At present, the chemotherapy of advanced inoperable liver cancer is limited with serious side effects. Curcumin possesses multiple cancer preventive activities and low safety concerns. However, its poor solubility and instability in water pose significant pharmacological barriers to its clinical application. In this study, we presented a novel delivery system – the glycyrrhetinic acid modified curcumin-loaded cationic liposomes (GAMCLCL) and investigated its antitumor activities on HepG2 cells in vitro and in H22 tumor-bearing mice. The experimental results demonstrated that GAMCLCL was a cationic liposome and could be Intravenous administration. Compared to free curcumin, GAMCLCL exhibited stronger antitumor activities in vitro and in vivo. The antitumor results of GAMCLCL after intravenous administration were very similar to those after intratumoral administration. The main activities of GAMCLCL and curcumin included inhibition of HepG2 cell proliferation, inhibition of tumor growth, reduction of tumor microvascular density, down-regulation of the expression of VEGF protein, and up-regulation of the expression of Caspases3 protein in H22 tumor tissues. Furthermore, GAMCLCL improved the parameters of WBC, RBC, ALT, CRE, LDH of H22 tumor-bearing mice. Curcumin is a nontoxic natural compound with definite antitumor activities, its antitumor effects can be enhanced by preparation of GAMCLCL.

Liver fibrosis is a wound healing response initiated by inflammation responding for different iterative parenchymal damages caused by diverse etiologies. Immune cells, which exert their ability of either inducing injury or promoting repair, have been regarded as crucial participants in the fibrogenic response. A characteristic feature of the fibrotic microenvironment associated with chronic liver injury is aberrant activation of hedgehog (Hh) signaling pathway. Growing evidence from a number of different studies in vivo and in vitro has indicated that immune-mediated events involved in liver fibrogenesis are regulated by Hh signaling pathway. In this review, we emphasize the impacts of injury-activated Hh signaling on liver fibrogenesis through modulating repair-related inflammation and focus on the regulatory action of aberrant Hh signaling on repair-related inflammatory responses mediated by hepatic classical and non-classical immune cell populations in the progression of liver fibrosis. Moreover, we also assess the potentiality of Hh pathway inhibitors as good candidates for anti-fibrotic therapeutic agents because of their immune regulation actions for fibrogenic liver repair. The identification of immune-modulatory mechanisms of Hh signaling pathway underlying the fibrotic process of chronic liver diseases might provide a basis for Hh-centered therapeutic strategies for liver fibrosis.