Abstract
Background:
Patients undergoing surgical resection of hepatocellular carcinoma (HCC) are at risk of recurrence; however, the underlying mechanism remains poorly understood.
Methods:
Through the analysis of gene expression profiles in tumour and matched normal tissues from patients with hepatocellular carcinoma (HCC), we identified differences in interleukin-11 (IL-11) expression. Further, we used genetic mouse, orthotopic tumour, chemically induced, and orthotopic allograft models to study the correlation between IL-11 and postsurgical recurrence. Additionally, we conducted a series of experiments, including histology and immunohistochemistry analysis, three-dimensional culture, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to investigate the role of IL-11-signal transducer and activator of transcription 3 (STAT3) signaling in HCC recurrence.
Findings:
We demonstrate that IL-11 levels increase after surgery, triggering HCC outgrowth. Accordingly, pharmacological blocking of IL-11-STAT3 signaling in model systems significantly alleviates tumour cell proliferation and suppresses postsurgical recurrence of HCC tumours.
Interpretation:
These data demonstrate that IL-11 has a central role in postsurgical HCC recurrence, and that inhibition of IL-11-STAT3 signaling is a potential therapeutic strategy to prevent recurrence. FUND: Natural Science Foundation of China.
Keywords:
Hepatocellular carcinoma; IL-11-STAT3 signaling; Napabucasin; Recurrence; Surgical resection.