Aim
To investigate the role of iodine-125 (125 I) combined with epirubicin (EPI) in inhibiting hepatocellular carcinoma (HCC) growth and promoting apoptosis.
Conclusion
EPI combined with 125 I induced apoptosis and inhibited the proliferation of HCC cells by LL-37 downregulating the WNT pathway.
Methods
Both in vivo and in vitro experiments were conducted. CCK-8 assay was performed to determine the cells viability after EPI treatment. HepG2 and SMMC7721 cells were treated with EPI or 125 I or in combination. Colony formation assays were performed to verify the antiproliferation effect. Annexin V-FITC/PI, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, and western blotting were performed to analyze cellular apoptosis. Scratch wound healing assays and transwell assays were used to examine migration following different treatments. An isobaric tag for relative and absolute quantitation analysis was used to detect changes in protein expression after 125 I treatment, identifying the potential mediating protein cathelicidin (LL-37). LL-37 protein and WNT pathway-related proteins were detected by western blotting in SMMC7721 and HepG2 cells. Mice were treated with 125 I and EPI to evaluate whether EPI enhanced the antitumor effect of 125 I.
Results
EPI promoted 125 I-induced apoptosis and reduced the proliferation of HepG2 and SMMC7721 cells. EPI also prevented the migration of HepG2 and SMMC7721 cells. EPI combined with 125 I may interfere with the WNT signaling pathway by decreasing LL-37 to inhibit HCC development. The antitumor effects of EPI with 125 I were verified in mice.