NADPH oxidase NOX4 inhibitor regulates the formation and mechanism of hepatoma related fibroblasts / 中国临床药理学与治疗学

ABSTRACT

AIM: To study the effect and mechanism of glx351322, an inhibitor of NADPH oxidase (NOX4), on the formation of tumor associated fibroblasts (CAFs). METHODS: NIH3T3 cells were co-cultured with H22 cells. 5 μm (IC50) GLX351322 cells were pretreated with NIH3T3. After PI staining, flow cytometry was used to detect the change of cell cycle, immunofluorescence staining was used to detect the expression of CAFs markers α-SMA and FAP, Western blot was used to detect the expression of CAFs markers α-SMA, Desmin, FAP, TSP-1, FSP, CyclinD, TGF-β1 and Smad1.After H22 was used to construct tumor bearing mice model, GLX351322 was used for treatment,Immunohistochemical staining was used to detect the expression of α-SMA and CAFs in tumor tissue. RESULTS:GLX351322 pretreatment could inhibit the proliferation of NIH3T3, decrease cell viability and change cell cycle. At the same time, it could down-regulate the expression of α-SMA, desmin, FAP, TSP-1, FSP, CyclinD, and TGF-β signal was inhibited. GLX351322 also significantly inhibited the expression of α-SMA and CAFs markers in tumor mice. CONCLUSION: GLX351322, a NOX4 inhibitor, can inhibit the formation of tumor-related fibroblasts, which is related to the inhibition of TGF-β signal.