BackgroundLung cancer is the leading cause of cancer deaths worldwide, with a five-year overall survival rate of only 15%. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein inhibiting PP2A in many human malignancies. However, whether CIP2A can be a new drug target for lung cancer is largely unclear.Methodology/Principal FindingsNormal and malignant lung tissues were derived from 60 lung cancer patients from southern China. RT-PCR, Western blotting and immunohistochemistry were used to evaluate the expression of CIP2A. We found that among the 60 patients, CIP2A was undetectable or very low in paratumor normal tissues, but was dramatically elevated in tumor samples in 38 (63.3%) patients. CIP2A overexpression was associated with cigarette smoking. Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. Intriguingly, we found a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells.Conclusions/SignificanceOur findings strongly indicate that CIP2A could be an effective target for lung cancer drug development, and the therapeutic potentials of CIP2A-targeting agents warrant further investigation.

Polypeptides with short chains of amino acid monomers have been widely applied in the clinic because of their various biological functions. However, the easily‐inactivated characteristics and burst releasing of the peptides limit their application in vivo. Here, a novel osteogenic polypeptide hydrogel (GelMA‐c‐OGP) is created by co‐cross‐linking template photo‐cross‐linked gelatin (GelMA) with photo‐cross‐linkable osteogenic growth peptides (OGP) using ultraviolet radiation. GelMA enables the formation of hydrogel with photo‐cross‐linkable OGP with good mechanical properties and also promotes bone regeneration. GelMA‐c‐OGP hydrogel accelerates the bone formation procedure of osteogenic precursor cells by significantly enhancing the expression of osteogenic‐related genes BMP‐2, OCN, and OPN, and increasing the precipitation of calcium salts in osteoblasts. Similarly, GelMA‐c‐OGP hydrogel promotes bone regeneration in vivo. Furthermore, it is observed that more collagen fibers connect cortical bones in the GelMA‐c‐OGP implanted group than the control group by hematoxylin‐eosin and immunohistochemical staining of Collagen I and TGF‐β. The co‐cross‐linked OGP polypeptide converts from liquid to solid hydrogel with transient UV light in situ, which also can strengthen the mechanical property of the defect bone and avoid burst osteogenic peptide, releasing during the bone defect healing period. Overall, this hydrogel delivering system has a significant impact on bone defect healing compared with traditional methods.

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This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.