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The clinical treatment of hepatocellular carcinoma has been hindered due to the drug resistance and heterogeneity of tumor cells. A new therapy strategy combined chemo drugs and molecular-targeted drugs is considered to be promising for conquering these challenges. However, the different pharmacokinetic profiles, hydrophobicity and systemic toxicity of these drugs may still cause serious challenges to the clinical applications of this combination therapy. In this study, smart sorafenib (SF) and doxorubicin (DOX)-loaded nanodroplets (SF/DOX-NDs) were fabricated to solve the above issues. The liquid-to-gas phase transition of SF/DOX-NDs could function as a cavitation nucleus to boost drug release and increase cellular uptake after exposure to therapeutic ultrasound (TUS) irradiation. Additionally, this strategy has a therapeutic effect to induce apoptosis and inhibit the proliferation, migration, and invasion of hepatoma cells. Furthermore, the intense cavitation of SF/DOX-NDs at the tumor site could disrupt microvessels, which is beneficial for tissue-penetrating drug delivery inside tumors. Consequently, tumor angiogenesis was reduced, and tumor growth was remarkably inhibited by SF/DOX-NDs. These results indicated that combination therapy using SF/DOX-NDs may offer a promising approach to achieve effective HCC therapy with low side effects.

RAP1B is a small GTPase, which regulates multiple cellular processes. Up-regulation of RAP1B has been observed in several cancer types. Although previous study has shown that miR-518 inhibited the proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells possibly by targeting RAP1B, the expression pattern and the functions of RAP1B in ESCC are not fully understood. Here, we have fund that the expression of RAP1B was up-regulated in ESCC clinical samples. Gain-of-function and loss-of-function assays demonstrated that RAP1B promoted the growth, migration and metastasis of the ESCC cells. Moreover, the mechanism study showed that RAP1B interacted with DVL2, an important upstream regulator for beta-catenin/TCF signaling, and activated beta-catenin/TCF signaling. Taken together, our study demonstrated the oncogenic roles of RAP1B in ESCC, and suggested that RAP1B might be a therapeutic target., (Copyright © 2017 Elsevier B.V. All rights reserved.)