Hepatocellular carcinoma results in a high risk of second primary
malignancies and has prominent morbidity and mortality. There is a lack of effective treatment and prognosis is poor. Therefore, effective drugs need to be discovered.
Carrimycin is a 16-member
macrolide antibiotic with anticancer activity, and monomeric isovalerylspiramycin I is a main component. The aim of this study was to determine the anti-
tumor effects of
carrimycin and monomeric isovalerylspiramycin I on
hepatocellular carcinoma through in vivo and in vitro experiments. In vitro, changes in cellular proliferation, migration, invasion, and apoptosis were analyzed by MTT, colony formation, EdU labeling, wound-healing,
matrigel transwell invasion, and flow cytometric assays using SK-Hep1, Hep3B, SNU-354, SNU-387
hepatocellular carcinoma cell lines. Western blotting and RT-PCR were used to detect the effects of
carrimycin and monomeric isovalerylspiramycin I on the expression levels of
vascular endothelial growth factor (
VEGF) and
programmed death ligand 1 (PD-L1). Nude mice were subcutaneously transplanted with SK-Hep1 cells or C57BL/6J mice were orthotopically transplanted with hepatocarcinoma H22 cells.
Tumor volume, pathological changes in
tumor tissues, and the concentration of
VEGF in mouse serum were measured
after treatments.
Carrimycin and monomeric isovalerylspiramycin I dose-dependently inhibited
hepatocellular carcinoma cell viability, colony formation, and DNA replication. These agents markedly suppressed migration and invasion and promoted apoptosis of the cell lines. Western blotting and RT-PCR demonstrated that
carrimycin and monomeric isovalerylspiramycin I reduced
VEGF and
PD-L1 protein and
mRNA levels in a dose-dependent manner. In vivo studies further confirmed that
carrimycin and monomeric isovalerylspiramycin I could significantly inhibit
tumor growth,
tumor histopathological alterations, and the concentration of
VEGF in both mouse
tumor models. These results show that
carrimycin and monomeric isovalerylspiramycin I promoted apoptosis and inhibited proliferation, migration, and invasion of
hepatocellular carcinoma cells. Therefore, our discovery suggests anti-
tumor capacity for
carrimycin and monomeric isovalerylspiramycin I and provides data on potential new drugs for inhibiting
hepatocellular carcinoma.