Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways

Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells.The unique proline isomerase Pin1 activates numerous cancer pathways,but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown.Moreover,the applicability of Pin1 inhibitor-all-trans retinoic acid(ATRA)is limited due to its several drawbacks.Herein,uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles(ATRA-NPs)with high encapsulation efficiency,good cellular uptake,excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design.ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma.Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs.ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression.Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth,it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

A high-throughput study on endothelial cell adhesion and growth mediated by adsorbed serum protein via signaling pathway PCR array

The purpose of this paper is to utilize the signaling pathway polymerase chain reaction(PCR)arrays to investigate the activation of two important biological signaling pathways in endothelial cell adhesion and growth mediated by adsorbed serum protein on the surface of bare and titanium nitride(TiN)-coated nickel titanium(NiTi)alloys.First,the endothelial cells were cultured on the bare and TiN-coated NiTi alloys and chitosan films as control for 4 h and 24 h,respectively.Then,the total RNA of the cells was collected and the PCR arrays were performed.After that,the differentially expressed genes in the transforming growth factor beta(TGF-b)signaling pathway and the regulation of actin cytoskeleton pathway were screened out;and the further bioinformatics analyses were performed.The results showed that both TGF-b signaling pathway and regulation of actin cytoskeleton pathway were activated in the cells after 4 h and 24 h culturing on the surface of bare and TiN-coated NiTi alloys compared to the chitosan group.The activated TGF-b signaling pathway promoted cell adhesion;the activated regulation of actin cytoskeleton pathway promoted cell adhesion,spreading,growth and motility.In addition,the activation of both pathways was much stronger in the cells cultured for 24 h versus 4 h,which indicated that cell adhesion and growth became more favorable with longer time on the surface of two NiTi alloy materials.