RESUMO
Background: Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health. Niclosamide is an anti-helminthic drug that has received FDA approval. In drug repurposing screens, niclosamide was found to inhibit proliferative activity for a range of tumor types. Its functional effects in HNSC, however, have yet to be established. Methods: MTT and colony formation assays were used to explore the impact of niclosamide on the proliferation of HNSC cells, while wound healing and Transwell assays were employed to assess migration and invasivity. Flow cytometry and Western immunoblotting were respectively used to assess cellular apoptosis and protein expression patterns. An HNSC xenograft tumor model system was used to evaluate the in vivo antitumor activity of niclosamide, and immunofluorescent staining was employed to assess cleaved Caspase3 and Ki67 expression. The ability of niclosamide to prevent metastatic progression in vivo was assessed with a model of pulmonary metastasis. Results: These analyses revealed the ability of niclosamide to suppress HNSC cell migration, proliferation, and invasivity in vitro while promoting apoptotic death. From a mechanistic perspective, this drug suppressed Stat3 phosphorylation and ß-catenin expression, while increasing cleaved Caspase3 levels in HNSC cells and reducing Bcl-2 levels. Importantly, this drug was able to suppress in vivo tumor growth and pulmonary metastasis formation, with immunofluorescent staining confirming that it reduced Ki67 levels and increased cleaved Caspase3 content. Conclusion: In conclusion, these analyses highlight the ability of niclosamide to inhibit HNSC cell migration and proliferative activity while provoking apoptotic death mediated via p-Stat3 and ß-catenin pathway inactivation. Niclosamide thus holds promise for repurposing as a candidate drug for the more effective clinical management of HNSC.
RESUMO
Responsive materials and actuators are the basis for the development of various leading-edge technologies but have so far mostly been designed based on polymers, incurring key limitations related to sensitivity and environmental tolerance. This work reports a new responsive material, laser-printed carbon film (LPCF), produced via direct laser transformation of a liquid organic precursor and consists of graphitic and amorphous carbons. The high activity of amorphous carbon combined with the dual-gradient structure enables the LPCF to have a actuation speed of 9400° s-1 in response to the stimulus of organic vapor. LPCF exhibits a conductivity of 950 S m-1 and excellent resistance to various extreme environmental conditions, which are unachievable for polymer-based materials. Additionally, an LPCF-based all-carbon soft robot that can mimic the complex continuous backward somersaulting motions without manual intervention is constructed. The locomotion velocity of the robot reaches a value of 1.19 BL s-1, which is almost one to two orders of magnitude faster than that of reported soft robots. This work not only offers a new paradigm for highly responsive materials but also provides a great design and engineering example for the next generation of biomimetic robots with life-like performance.
