Suppression of hepatocellular carcinoma by mycophenolic acid in experimental models and in patients
2019
Background. Tumor recurrence is a major complication following liver transplantation (LT) as treatment for hepatocellular
carcinoma (HCC). Immunosuppression is an important risk factor for HCC recurrence, but conceivably may depend on the
type of immunosuppressive medication. Mycophenolic acid (MPA) is a currently widely used immunosuppressant. This study
investigated the effects of MPA on HCC. Methods. Three human HCC cell lines and organoids from mouse primary liver
tumor were used as experimental models. MTT, Alamar Blue assay, cell cycle analysis, colony formation, and [3H]-thymidine
assays were performed. An LT database was used for retrospective analysis of the effect of mycophenolate mofetil, the
prodrug of MPA, on HCC recurrence. Results. With clinically achievable concentrations, MPA effectively inhibited HCC cell
proliferation and single-cell colony-forming unit. In short-term experiments, MPA effectively elicited S phase arrest in HCC
cell lines. In addition, the initiation and growth of liver tumor organoids were effectively inhibited by MPA. Most importantly,
the use of mycophenolate mofetil in patients with HCC-related LT was significantly associated with less tumor recurrence
and improved patient survival. Conclusions. MPA can specifically counteract HCC growth in vitro and tumor recurrence
in LT patients. These results warrant prospective clinical trials into the role of MPA-mediated immunosuppression following
LT of patients with HCC.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
39
References
9
Citations
NaN
KQI