STING-mediated Syk Signaling Attenuates Tumorigenesis of Colitis‑associated Colorectal Cancer Through Enhancing Intestinal Epithelium Pyroptosis

Background Stimulator of interferon genes (STING) has essential functions in the immune responses and can induce cancer cell apoptosis. However, it is not completely clear how STING plays a role in colitis-associated colorectal cancer (CAC) and whether it can trigger pyroptosis during the tumorigenesis of CAC. Methods To investigate the role of STING-modulated pyroptosis in the development of CAC, STING knockout and Wild type mice were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to establish a murine CAC model. STING pharmacological agonist was used to further study the functions of STING signaling in the tumorigenesis. Moreover, STING endogenous ligand was employed to verify the effects of STING in human colon cancer cells. Results STING deficiency mice were more susceptible to CAC by reducing pyroptosis of tumor cells, whereas overactivation of STING with the agonist suppressed tumorigenesis of CAC. STING also managed CAC development by modulating tumor cells proliferation, adhesion, and invasion, as well as inflammatory response. The ex vivo studies indicated that STING could induce pyroptosis via spleen tyrosine kinase (Syk), and Syk knockdown weakened such pyroptotic tumor cells death. In addition, the visible physical interaction between STING and Syk was observed in colorectal tumor samples of CAC patients. Conclusions STING-mediated Syk signaling may regulate the tumorigenesis of CAC by modulating pyroptosis of tumor cells, and modulation of STING/Syk serves as a novel therapeutic strategy for CAC therapy.

Preparation of β-CD-DPPE-Dox Nanomedicine and Its’ Application as the Anticancer and Antitumor Drug

β-CD-DPPE molecule was synthesized through the conjugation of β-CD-NH2 and the DPPE molecule, and its’ water-solubility was more excellent than the traditional phospholipid molecule. The spherical micelles was formed by β-CD-DPPE molecule in aqueous solution, and the β-CD-DPPE-Dox nanomedicine can be prepared through loading Dox (Doxorubicin) into the micelles, and the Dox loading ratio was about 82.3 ± 7.27%. At the same time the Dox release behavior from the nanomedicine was sustained-release and pH controlled release, and the release test in vitro showed that the release rate of the Dox at the lower pH was faster than that of normal pH (pH = 7.4), which indicated that the rate of release in the tumor microenvironment is faster than in the normal tissue. Biological test showed that the micelles was low cytotoxicity, and the cytotoxicity of β-CD-DPPE-Dox nanomedicine was lower than the Dox under the same Dox concentration, and the β-CD-DPPE-Dox nanomedicine could effectively induce cancer cell apoptosis and inhibit the tumor growth.

Facile synthesis of highly uniform selenium nanoparticles using glucose as the reductant and surface decorator to induce cancer cell apoptosis

Herein, we demonstrated a new and facial synthesis of highly uniformed SeNPs using glucose as the reductant and surface decorator. Glu–SeNPs induced cancer cell apoptosisviainduction of apoptosis by triggering intracellular ROS overproduction and mitochondrial dysfunction.

Photothermal and photodynamic therapy reagents based on rGO–C6H4–COOH

A photothermal and photodynamic therapy reagent based on rGO–C6H4–COOH was developed, which could effectively induce cancer cell apoptosis.

Anti-hepatoma activity of the stiff branched β-d-glucan and effects of molecular weight

The water soluble β-d-glucan AF1 with short branches isolated from Auricularia auricula-judae exhibited significant anti-hepatoma activities, and it was confirmed that AF1 had stiff chains and could induce cancer cell apoptosis and anti-angiogenesis through activating immune responses.