Saikosaponin‐b2 inhibits tumor growth and inflammation of hepatocellular carcinoma by regulating STK4 / IRAK1 / NF‐κB signaling in H22 tumor‐bearing mice

Abstract

The tumor suppressor serine/threonine‐protein kinase 4 (STK4) may regulate inflammatory signaling in macrophages and thereby protective against inflammation‐associated HCC. Saikosaponin (SS)‐b2, a major bioactive ingredient of saikosaponins from Chinese thorowax root, exhibited anti‐cancer, anti‐inflammatory, anti‐viral, and anti‐oxidant activity. However, the anti‐tumor effect and its signaling mechanism of SS‐b2 on H22 hepatocellular carcinoma remain unknown. This study investigated the anti‐tumor effect of SS‐b2 on H22 hepatocellular carcinoma by regulating STK4/IL‐1 receptor associated kinase 1(IRAK1)/NF‐κB signaling. BALB/c mice were randomly divided into model group (normal saline, 10mL·kg−1·d−1, i.p.), different dose SS‐b2 group (3, 6, 12 mg·kg−1·d−1, i.p.) and doxorubicin group (DOX, 2 mg·kg−1, once every other day, i.p.). The mice were administered for 10 days. The results showed that SS‐b2 had a significant anti‐tumor effect on H22 xenograft mice. The tumor inhibiory rate of SS‐b2 was 16.8%, 32.7% and 55.8% respectively at 3 mg·kg−1, 6 mg·kg−1 and 12 mg·kg−1 dose. SS‐b2 decreased the spleen index in a dose‐independence way but it decreased the liver index only at 12 mg·kg−1 dose. SS‐b2 also significantly reduced the levels of AST and ALT in serum at 6 mg·kg−1 and 12 mg·kg−1. HE Staining revealed that SS‐b2 significantly attenuated the pathological morphology changes. Tumor tissue showed large necrotic, nucleus lysis and vacuole areas in mice with SS‐b2 treatment. Immunohistochemistry results showed that the positive expression of STK4 protein in tumor tissue increased however IRAK1 protein expression decrease significantly in SS‐b2 groups compared with the model group. Moreover, Western blot analysis also showed that the protein expression of STK4 increased whereas the expressions of IRAK1 and NF‐κB protein were decreased in tumor tissue, spleen, and serum in SS‐b2 treatment group. These results suggest that SS‐b2 exerts a significant anti‐tumor effect on H22 xenograft mice by regulating STK4/IRAK1/NF‐κB pathway.Support or Funding InformationThis study was supported by Science and Technology Key Research Fund funded projects of Henan Province, China (No. 142102310137), the Science and Technology Development Project of Luoyang City (No. 1603001A‐3).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.