STAT3 inhibitors(Zhejiang Chinese Medical University)

Targeting Nampt to modulate NAD + metabolism and exert antitumor effects has become a research hotspot in the field of cancer metabolism. But early clinical trials have only achieved modest results, primarily due to the need for improved efficacy and the occurrence of severe systemic adverse effects. Therefore, enhancing antitumor efficacy and reducing the adverse effects of Nampt inhibitors are urgent challenges. The research reveals that the Nampt inhibitor FK866 can induce ferroptosis in colorectal cancer cells via the NAD + /Stat3/Gpx4 signaling axis. Furthermore, the combination of FK866 and the Stat3 inhibitor C188‐9 demonstrates a strong synergistic antitumor effect. Importantly, a reactive oxygen species (ROS)‐responsive hydrogel that encapsulates FK866 and C188‐9 for in situ drug delivery, effectively reducing systemic side effects, is developed. Intriguingly, mass cytometry time‐of‐flight (CyTOF) analysis indicates that the combined treatment with FK866 and C188‐9 exerts antitumor effects by increasing the infiltration of CD8 + T cells and neutrophils into the tumor, as well as enhancing the expression of immune‐regulatory molecules, including IFN‐γ, IL‐10, and perforin. Thus, this localized treatment not only minimizes systemic adverse effects, but also markedly amplifies antitumor efficacy through the modulation of both tumor cells and the tumor immune microenvironment, representing a promising antitumor treatment strategy.

Cellular impedance-sensing technology has not been widely used to determine ionizing radiation- induced apoptosis.

A cellular electrical impedance-sensing system, including host software and a hardware system consisting of 29 microelectrode arrays, was constructed by us. After group processing, U87 cells were inoculated onto the electrode chips, and changes in the electrical impedance of each group of cells were monitored in real-time. Apoptosis levels in each group of cells were determined using conventional techniques and compared with the trend of their corresponding changes in electrical impedance.

The electrical impedance profile of U87 cells could be used to monitor apoptosis levels in real-time. Ionizing radiation and the STAT3 inhibitor WP1066 both induced apoptosis in U87 cells by activating the Bcl-2/BAX/Caspase-3 signaling pathway. WP1066 promoted apoptosis in glioblastoma cells by preventing the nuclear translocation of pSTAT3, and radiation-induced apoptosis began earlier than WP1066-induced apoptosis.

This novel study establishes a practical and theoretical foundation for radiation electrophysiology research by demonstrating that the cellular impedance-sensing system based on microelectrode arrays can detect ionizing radiation-induced and drug-induced glioblastoma cell death in real-time.