Honokiol Inhibits Stemness in Pancreatic Cancer via Downregulating c‐Met Expression

Due to its high recurrence and metastasis rates, the prognosis of pancreatic cancer (PC) patients is extremely poor. Cancer stem cells (CSCs) are the major source of occurrence and progression of PC, suggesting that targeting pancreatic CSC stemness may provide therapeutic benefits. This study aims to clarify the mechanisms by which Honokiol (HNK) inhibits the stemness of pancreatic cancer. The expression of c-Met and downstream molecules was investigated based on public databases and also confirmed by the immunohistochemistry (IHC) staining of human tissues. Colony formation assay and sphere formation assay were conducted to verify the effect of HNK on the proliferation and stemness of PC cells. A subcutaneous transplanted tumor model of BALB/c nude mice was established to explore the effect of HNK on modulating the tumor growth of PC in vivo. c-Met expression was significantly elevated in PC tissues versus normal pancreas tissues, and the high level of c-Met was positively correlated with poor prognosis of PC patients. Overexpression of c-Met significantly enhanced the proliferation and stemness of cancer cells, whereas HNK treatment reversed these effects. Critically, HNK suppressed tumor growth in vivo by downregulating c-Met. Our study reveals that HNK reduced the proliferation and stemness of PC cells via suppressing the c-Met overexpression. These findings provide a potential therapeutic method for PC, offering new hope for improving patients' outcomes.