Hepatocellular Senescence Linked to Liver Cancer Development: Sirolimus Shows Preventive Potential in Preclinical Study
A new study published in Human Cell by researchers at the University of Nottingham highlights the role of hepatocellular senescence in the progression to hepatocellular carcinoma (HCC). The study further demonstrates that sirolimus, an mTOR inhibitor, can prevent HCC development by suppressing the secretion of senescence-associated secretory phenotype (SASP) factors.
The team analyzed liver biopsy specimens from patients with cirrhosis and HCC, focusing on the expression of the senescence marker p16. The results indicated a positive correlation between high p16 expression and increased HCC risk. Using the STAM™ mouse model of MASH-HCC, the study evaluated the preventive effects of sirolimus administered at early (from 4 weeks of age) and late (from 12 weeks of age) stages. Compared to placebo controls, early sirolimus treatment significantly reduced both the number and size of HCC nodules. Additionally, sirolimus effectively decreased the expression of key SASP factors including TNF-α, IL-1β, IL-2, and CXCL15.
This research suggests that hepatocellular senescence plays a critical role in liver cancer pathogenesis and identifies sirolimus as a potential preventive intervention by targeting the inflammatory microenvironment. These findings provide a strong rationale for further clinical investigation.