Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases.
Introduction and objectives The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrosis. The beneficial effects of fibroblast growth factor (FGF) 19 on liver fibrosis were recently reported. The S. miltiorrhiza as well as S. miltiorrhiza derived bioactive chemical components has shown prominent antifibrotic effects in liver fibrosis but the mechanism is still not fully understood. We aimed to investigate the bioactive compounds derived from S. miltiorrhiza which exerts antifibrotic effects in HSCs via regulating FGF19. Materials and methods FGF19 level in culture media was determined by enzyme-linked immunosorbent assay. Cell proliferation was measured by Cell Counting Kit-8 assay. Further, mRNA and protein expressions were assessed by quantitative polymerase chain reaction and western blotting, respectively. Knocking down of FGF receptor 4 (FGFR4) by transfection with siRNA was used to confirm the role of FGF19/FGFR4 signaling. Results Using the human HSC cell line LX-2, we screened several natural products and found that bioactive compounds isolated from Salvia miltiorrhiza , particularly salvianolic acid B, strongly upregulated FGF19 secretion by LX-2 cells. We further showed that salvianolic acid B inhibited lipopolysaccharide (LPS)-induced HSC proliferation and activation. LPS treatment may also reduce the mRNA and protein levels of FGF19 and its receptor FGFR4. Salvianolic acid B treatment restored the impaired expressions of FGF19 and FGFR4. Finally, FGFR4 knockdown abolished the antifibrotic effects of salvianolic acid B in the LPS-induced HSC activation model. Conclusions Salvianolic acid B prevented LPS-induced HSC proliferation and activation by enhancing antifibrotic FGF19/FGFR4 signaling.
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